Ophthalmic adverse effects of BRAF inhibitors

To determine the frequency, characteristics, and clinical course of ophthalmic side effects associated with systemic BRAF inhibitor therapy. Medical records of patients taking BRAF inhibitors for the treatment of systemic malignances at Mayo Clinic, Rochester from 01/01/2010 to 08/30/2021, were retrospectively reviewed. Of 901 patients, 14 (1.6%) patients experienced an ophthalmic side effect. Mean age at presentation of the side effect was 60 years (median 59, range 50-80) and 11 (79%) were male. The most common side effect was uveitis in 7 (50%) patients, followed by dry eye in 4 (29%) patients, and central serous chorioretinopathy in 2 (14%) patients, with singular cases of cranial nerve VI palsy and conjunctival edema. A comparison between individual BRAF inhibitors (vemurafenib vs. dabrafenib vs. encorafenib) revealed that patients taking encorafenib had a shorter interval to any ophthalmic adverse event (mean 55.6 vs. 9.8 vs. 4.0 months, p  =  0.03) and were the only patients to experience documented dry eye syndrome (DES) in this series. Outcomes were known in 13 (93%) patients, and ophthalmic adverse effects resolved or were controlled without discontinuing therapy in 10 (77%). Uveitis was successfully treated with topical corticosteroids in 4 patients, while 3 patients with refractory uveitis (2 with panuveitis and 1 with unspecified uveitis) required discontinuation of BRAF inhibitor therapy. Ophthalmic adverse events related to systemic BRAF inhibitor use are rare, with estimated frequency of 1.6%. Most events can be treated with local ophthalmic therapy. BRAF inhibitors provide life-saving therapy, and their discontinuation should be avoided.