INTRODUCTION: The combination of BRAF and MEK inhibitors (BRAFi and MEKi) is a key treatment for stage III and IV BRAF-mutated cutaneous malignant melanomas. While ocular adverse effects are common, few studies are using real-world data to characterize these complications. METHODS: This retrospective observational study at Hospital de Santa Maria, Lisbon, aimed to conduct a comprehensive analysis of all patients with BRAF-mutated cutaneous stage III and IV malignant melanoma who were by protocol referred for ophthalmic screening before, during and after undergoing therapy with BRAFi and MEKi between 2016 and 2023. Demographic and clinical data were collected, with statistical analysis using chi-square, Fisher's exact tests, and t-tests. RESULTS: Thirty-two patients were included, 17 (53.1%) of whom are female. The average age of the sample is 60.8 ± 12.3 years. Twenty-one (65.6%) patients underwent treatment with dabrafenib + trametinib (D+T), seven with vemurafenib + cobimetinib (V+C) and four with encorafenib + binimetinib (E+B). The median time between melanoma diagnosis and treatment onset was 9.3 months (IQR 3.6-17.3). The median ophthalmological follow-up was 6.8 months (IQR 3.3-13.5). Nine patients (28.1%) presented ophthalmological adverse effects: serous retinal detachment in seven (21.9%), five of which presented serous detachment of the fovea; anterior uveitis in two (6.3%); and panuveitis with papillitis in one (3.1%). The majority (88.9%) of patients with complications presented bilateral involvement and in 2/3 of cases, patients were asymptomatic. There was a suspension of the therapeutic regimen only in one patient (11.1%). The median interval between the start of therapy and the emergence of complications was 57.8 days (IQR 25.9-241.8). There was a difference (p = 0.010) in the proportion of adverse effects between the three regimens (D+T:14.3% E+B:25.0% V+C:71.4%), particularly between D+T and V+C (p = 0.009). The incidence of adverse effects did not appear to depend on gender (p = 1.000), age (p = 0.367) or melanoma stage (p = 0.303). There is no statistically significant association between the occurrence of complications and mortality (p = 0.694). CONCLUSION: Despite a high incidence of ocular complications with BRAFi and MEKi, most patients remain asymptomatic, highlighting the need for regular ophthalmological monitoring, especially in the first 3 months, to detect and manage complications early.
Lobo et al. (Sun,) studied this question.