Mineralocorticoid receptor expression and the effects of the mineralocorticoid receptor antagonist spironolactone in a murine model of graft-versus-host disease.

Purpose: The topical administration of spironolactone, a mineralocorticoid receptor antagonist (MRA) improves dry eye symptoms in patients with ocular graft-versus-host disease (GVHD); however, the detailed mechanism remains unclear. This study aimed to investigate the effects of spironolactone eyedrops on the ocular surface using a chronic GVHD (cGVHD) mouse model and to determine the expression of the mineralocorticoid receptor (MR).

Methods: A cGVHD mouse model was established by allogeneic bone marrow transplantation (BMT) from B10.

Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease.

Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation.

15-Gene Expression Profile and as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/ classifier.MATERIALS AND METHODSThis study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers.

Consensus Guidelines for Ocular Surveillance of von Hippel-Lindau Disease.

Purpose: To develop guidelines for ocular surveillance and early intervention for individuals with von Hippel-Lindau (VHL) disease.

Design: Systematic review of the literature.

Participants: Expert panel of retina specialists and ocular oncologists.

Multicentre analysis of nucleic acid quantification using aqueous humour liquid biopsy in uveal melanoma: implications for clinical testing.

Objective: Uveal melanoma (UM) tumour biopsy is limited by size and intratumour heterogeneity. We explored the potential of aqueous humour (AH) liquid biopsy for UM by quantifying analytes in samples collected at diagnosis and after brachytherapy to look for clinical correlations with tumour features.

Design: Case-series study.

Ocular Toxicity Profile of Targeted Cancer Therapy (TCT) at a US Tertiary Cancer Center.

Purpose:  Targeted cancer therapy (TCT) is a significant advancement in oncology with promising survival improvement in patients with cancer and remarkable effects on various cancers. There is evidence suggesting a connection between specific TCT classes and the occurrence of immune-related adverse events (irAEs). Our study aims to investigate the potential ocular toxicities of different classes of TCT, provide a better understanding of these toxicities, and aid in the future development of screening and management recommendations for ocular irAEs.

Association of choroidal invasion with retinoblastoma survival rates.

Purpose: To assess the impact of varying levels of choroidal invasion on survival from retinoblastoma.

Methods: A retrospective nationwide analysis of retinoblastoma cases diagnosed between 2004-2016 using the Surveillance, Epidemiology, and End Results database was conducted. Overall survival, cause-specific survival, and all-cause mortality risk were assessed as primary outcomes.

Highlights on Ocular Toxicity of Immune Checkpoint Inhibitors at a US Tertiary Cancer Center.

Introduction: Immune checkpoint inhibitors (ICIs) have improved prognosis in advanced malignancies; however, they may be associated with extensive ocular immune-related adverse events (irAEs) that are sight threatening. Our study aimed to identify the presentation, characteristics, management, and clinical outcomes of ocular irAEs.

Methods: In this retrospective, observational case series, we reviewed the medical records of 1280 patients at a large US tertiary cancer center between 2010 and 2020.

Second Primary Malignancies in Patients With Melanoma Subtypes: Analysis of 120,299 Patients From the SEER Database (2000-2016).

Purpose: Evaluate incidence of second primary malignancies (SPM) after non-acral cutaneous melanoma (NACM), acral lentiginous melanoma (ALM), mucosal melanoma (MM), and uveal melanoma (UM).

Patients And Methods: First primary NACM, ALM, MM, and UM cases diagnosed 2000-2016 were extracted from SEER. Seer*Stat was used to calculate excess absolute risks (EAR) and standardized incidence ratios (SIR) of SPMs relative to a matched cohort from the general population.

Immune-Related Oral, Otologic, and Ocular Adverse Events.

Emerging immunotherapeutic agents, including immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1), have revolutionized cancer treatment. The first immune checkpoint inhibitor (ICI) ipilimumab, an anti-CTLA-4, was approved in 2011. Since then, the US Food and Drug Administration (FDA) has approved more than half a dozen immune checkpoint inhibitors to treat various malignancies.

Metastatic Risk Factors Associated with Class 1A Uveal Melanoma Patients.

In uveal melanoma (UM), gene expression profiling (GEP) is commonly used to classify metastatic risk into three groups (Class 1A, 1B, and 2). Class 1A patients have a lower metastatic risk of 2% at 5 years compared to other groups. We aimed to describe clinical features associated with the development of metastasis in this low-risk group.

Overview of Ocular Side Effects of Selinexor.

Background: The aim of this review is to elucidate the type and frequency of ocular adverse events associated with selinexor with a goal to quantify the occurrence of these events in our investigator-initiated trial.

Methods: We retrospectively reviewed medical records of 174 patients treated with at least one dose of selinexor in combination with multiple standard chemotherapy or immunotherapy agents between July 2015 and July 2020 at a comprehensive cancer center in the U.S.

Reversible HER2 antibody-drug conjugate-induced ocular toxicity.

Purpose: To report 3 cases of reversible epitheliopathy induced by A166-a human epidermal growth factor receptor (HER2)-targeted antibody-drug conjugate (ADC) therapy for resistant HER2 tumours.

Methods: Advanced HER2 tumour patients were enrolled in A166 phase I/II clinical trial using Bayesian logistic regression model dose escalation. Key exclusion criteria were ≥grade 2 (G2) corneal pathology, severe organ disease, and other cancer therapy within 4 weeks.

Targeted Cancer Therapy and Its Ophthalmic Side Effects: A Review.

Targeted cancer therapy agents are the latest development in cancer therapeutics. Although the spectrum of their use continues to expand, ocular side effects are frequently encountered with the use of cancer therapeutics. This review describes the ocular side effects of targeted cancer therapy agents.

Response criteria for intraocular retinoblastoma: RB-RECIST.

Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response-such as progression-free survival-to evaluate the efficacy of treatment agents.

Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy.

Background: To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies.

Methods: Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM.

Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study.

Purpose: Metastatic uveal melanoma has poor overall survival (OS) and no approved systemic therapy options. Studies of single-agent immunotherapy regimens have shown minimal benefit. There is the potential for improved responses with the use of combination immunotherapy.