Purpose: To quantify the risk of ocular adverse events with immune Checkpoint inhibitors (ICIs) as reported to the Food and Drug Administration (FDA). Methods: Disproportionality analysis using data from U. S. FDA's Adverse Events Reporting System (FAERS) database 2003 to 2018. Data from pharmaceutical manufacturers, healthcare providers, consumers in the U. S., and post-marketing clinical trial reports from U. S. and non-U. S. studies. All cases of uveitis, dry eye syndrome, ocular myasthenia and eye inflammation with use of the following ICIs: atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab and pembrolizumab. Reported odds ratios (RORs) and corresponding 95% confidence intervals (CIs) were computed for all drugs as a group or as individual agents. Results: We identified 113 ocular adverse events for all ICIs of interest including uveitis, dry eye, ocular myasthenia and eye inflammation. Nivolumab had the highest number of adverse events (N ¼ 68) associated with use of the ICI. Nivolumab had the highest association with ocular myasthenia [ROR ¼ 22. 82, 95% CI (7. 18e72. 50)] followed by pembrolizumab [ROR ¼ 20. 17, 95% CI (2. 80e145. 20)]. Among all ICIs approved in North America, atezolizumab had the highest association with eye inflammation [ROR ¼ 18. 89, 95% CI (6. 07e58. 81)] and ipilmumab had the highest association with uveitis [ROR ¼ 10. 54, 95% CI (7. 30e15. 22)]. Conclusion: The results of this disproportionality analysis suggest use of ICIs is associated with an increase risk for ocular adverse reactions. Future epidemiologic studies are needed to better quantify these adverse events.

BACKGROUND: Immune Checkpoint inhibitors (ICIs) have promising clinical activity and are essential medications for patients with several malignancies. However, by deranging the immune system, these novel agents could lead to immune-related adverse events (IRAEs). Hepatotoxicity with Checkpoint inhibitors usually results in acute hepatitis or drug-induced liver injury. METHODS: This review article discusses the recent clinical evidence available regarding Checkpoint inhibitor-induced hepatitis and reviews an approach to their diagnosis and management. RESULTS: The rate of liver injury with ICIs varies between different Checkpoint inhibitors. It has been reported that the incidence of various grades of autoimmune hepatotoxicity with CTLA-4 inhibitors is between 3%-9%. The clinical characteristics of ICIs-induced hepatotoxicity are quite heterogeneous but they are usually in line with an autoimmune induced liver injury. Management of severe ICIs-related hepatitis should consist of termination of the ICI and treatment with corticosteroids. CONCLUSION: ICIs have improved patients’,outcomes with different forms of malignancy,however, ICIs-related liver damage is a clinically significant entity in these patients. All patients should be monitored carefully for IRAEs while undergoing treatment with ICIs.

The management of conjunctival melanoma is challenging due to the more frequent local recurrence and metastasis compared to other conjunctival neoplasms. Locally advanced conjunctival melanoma may require an orbital exenteration, and treatment options for metastatic conjunctival melanoma have been limited until recently. This review aims to provide comprehensive updates on immunotherapy for conjunctival melanoma, focusing on immune Checkpoint inhibitors. We reviewed the available literature on the use of immunotherapy for the treatment of conjunctival melanoma. Systemic immunotherapy, particularly with Checkpoint inhibitors, has recently been reported to have improved outcomes for patients with conjunctival melanoma. Immune Checkpoint inhibitors that are currently approved by the US Food and Drug Administration for melanoma include anti-PD-1 (nivolumab and pembrolizumab), anti-PDL-1 (avelumab and atezolizumab), and anti-CTLA-4 inhibitors (ipilimumab). Most recent reports described using immune Checkpoint inhibitors in patients with locally advanced conjunctival melanoma in an attempt to avoid orbital exenteration or in patients with metastatic conjunctival melanoma. Although the current data are limited to case reports and small case series, eye care providers should be aware of the potential role of immunotherapy for patients with locally advanced, recurrent, or metastatic conjunctival melanoma.

Background: Immune Checkpoint inhibitors (ICIs), including antiprogrammed cell death receptor-1, antiprogrammed cell death ligand-1, and anticytotoxic T-lymphocyte-antigen 4, have improved patients’ outcome in advanced malignancies. These agents are associated with immune-related adverse events, including skin toxicity, gastrointestinal toxicity, hepatotoxicity, renal toxicities, and endocrinopathies.Method: We retrospectively reviewed the electronic medical records of patients treated with ICIs for advanced malignancies from two tertiary cancer care centers in the Emirate of Dubai, United Arab Emirates (UAE), including Dubai Hospital and American Hospital from November 2015 to January 2019. The patients were identified through the hospital cancer registry. We retrospectively collected data regarding the subjects’ demographics, cancer type, type of ICIs, thyroid-related adverse events, and duration of treatment.Results: In the present paper, 43 patients received ICI and 19 (44%) developed thyroid dysfunctions. The median age of ICI-receiving subjects was 60 (27-80) years; 26 of them were male and 17 were female. Pembrolizumab was the most used agent (42%). Pretreatment thyroid functions were normal for all the patients. Following treatment initiation, 19 (44%) patients developed thyroid abnormalities, including overt hypothyroidism (n = 11, 57%), overt hyperthyroidism (n = 2, 11%), subclinical hypothyroidism (n = 4, 21%), and subclinical hyperthyroidism (n = 2, 11%). Thyroid abnormalities developed in 56% of them treated with Pembrolizumab and 37% treated with Nivolumab.Conclusion: Hypothyroidism was the most prevalent thyroid adverse event in the patients treated with ICIs in our study and the majority of thyroid dysfunction encounters took place in the first 6 weeks after ICI initiation. The treatment was well tolerated and there were no treatment-related discontinuations or deaths.