**4. Target therapies of proto-oncogene B-RAF and mitogen-activated protein kinase BRAF/MEK**

ICIs are not the only immunomodulatory medication associated with uveitis. Approximately 25–100% of patients treated with BRAF/MEK inhibitors develop ocular adverse effects [5]. These medications are primarily used in the treatment of melanoma. Nearly 50% of the patients with advanced melanoma have BRAF (V600E) mutations [19]. The MEK gene is closely connected to the BRAF gene, so drugs that target MEK also help with BRAF mutation melanomas. BRAF inhibitor drugs as monotherapy have shown high rapid response rates not previously seen in melanoma patients. However, the duration of responses is limited in most patients. The same occurs in MEK monotherapy. The combination of BRAF/MEK inhibitors has shown significant improvement in response rates [19]. BRAF inhibitors include vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi). MEK inhibitors approved are trametinib (Mekinist), cobimetinib (Cotellic), and binimetinib (Mektovi).

A cohort study by F. Dimitriou et al., published in 2021, investigated if the occurrence of uveitis under treatment with BRAF/MEK and ICI is more frequent than in a general population of patients without treatment for cutaneous melanoma and found that patients treated with BRAF/MEK inhibitors had a two-fold higher hazard of developing uveitis. Clinical findings were similar in patients treated with ICI and BRAF/MEK inhibitors. They do not specify treatments but state that the course was complicated in four of eleven patients requiring systemic steroids. No patients had to discontinue their cancer treatment due to the uveitis. There are minimal reports of BRAF/MEK clinical trials, which could account for an underreporting of rare adverse events, such as uveitis [5]. But as we gather more data, more information can be gathered, and more accurate treatment and diagnostic recommendations can be made.
