RESUMEN
In the last two decades, an increasing number of so-called molecular-targeted therapies have become available for the treatment of patients with advanced malignancies. These drugs have included inhibitors of proteins in the MAPK pathway, such as BRAF and MEK inhibitors, which are characterized by a distinct toxicity profile. The eye is particularly susceptible to adverse effects due to MEK inhibitors, and the term MEKAR (MEK-inhibitor-associated retinopathy) indicates the presence of subretinal fluid, mimicking central serous chorioretinopathy (CSC). The pathogenesis of the retinal alterations related to MAPK pathway inhibitors is still unclear, and questions are still open. The present study aims to assess the presence of retinal pigment epithelium alterations as predictive parameters for retinal toxicity, analyzing, at the same time, the chorioretinal vascular network in patients undergoing BRAF/MEK inhibitor treatment for different malignancies.
RESUMEN
PURPOSE: To evaluate choroidal vascularity index (CVI) in patients developing mitogen-activated protein kinase kinase (MEK) inhibitor-associated retinopathy (MEKAR). METHODS: In this prospective observational study, extensive ophthalmic examination was performed, including enhanced-depth-imaging-optical coherence tomography (EDI-OCT). EDI-OCT scans of patients receiving Cobimetinib, taken at baseline and at MEKAR manifestation, were considered for choroid analysis. Choroidal thickness (CT) was measured on high-resolution b-scans passing through the fovea at three different locations. Same scans were therefore imported for binarization into a previously reported software and CVI was calculated as the ratio of luminal area (LA) to total choroid area (TCA). RESULTS: When compared to baseline, eyes with MEKAR (14 eyes) did not show significative CT variation in subfoveal region (p = 0,57), 750-µm-nasal to the fovea (p = 0,08) and 750-µm-temporal to the fovea (p = 0,07). Similarly, there were no statistically significant differences for TCA (p = 0.54), LA (p = 0.85), stromal area (SA) (p = 0.13), LA/SA (p = 0.34) and CVI (p = 0.47). Best-corrected visual acuity was significantly reduced at fluid accumulation when compared to baseline values (p = 0.03), with complete recovery after fluid resolution (p = 0.73). CONCLUSION: Multiple parameters reflecting the status of the choroid seemed not influenced by Cobimetinib administration. Retinal pigment epithelium toxic disfunction likely represents the crucial step in MEKAR pathogenesis.