Serous retinopathy associated with MEK inhibition (binimetinib) for metastatic cutaneous and uveal melanoma

Abstract

 

Purpose

 

To analyse the clinical characteristics of a serous retinopathy associated with MEK inhibition with binimetinib for metastatic cutaneous melanoma (CM) and uveal melanoma (UM), and to study possible pathogenetic mechanisms that may lead to this retinopathy.

 

Methods

 

An extensive ophthalmic examination was performed in all patients, including Early Treatment of Diabetic Retinopathy Study (ETRDS) best-corrected visual acuity (BCVA) measurement, slit lamp examination, indirect ophthalmoscopy, fundus photography, and optical coherence tomography. In selected cases, additional examinations were performed, including central visual field analysis, fundus autofluorescence, fluorescein angiography, electro-oculography (EOG), and electroretinography (ERG). Blood samples were obtained from 3 CM and 3 UM patients to analyze the presence of autoantibodies against retinal and retinal pigment epithelium (RPE) proteins.

 

Results

 

Six CM (20%) and 2 UM patients (40%) reported visual complaints during the study. The mean time until the onset of visual complaints, which were mild and transient in all patients, was 6 days (range, <1 hour-3 weeks). On OCT, serous subretinal fluid (SRF) was detected in 77% of CM patients, and in 60% of UM patients. The SRF affected the fovea in 85% of 26 patients with SRF, while SRF was detected extrafoveally in 81% of patients. In 19 eyes of 11 patients an EOG was performed after the start of the binimetinib medication: 16 of these eyes (84%) developed SRF on OCT. Fifteen (94%) of these eyes showed an abnormal Arden ratio (<1.65), and 1 eye (6%) showed a subnormal Arden ratio (1.65-1.8). A broad pattern of anti-retinal antibodies was found in 3 CM and 2 UM patients. Anti-RPE-antibodies were detected in all 6 patients. Anti-bestrophin antibodies were detected in 3 patients.

 

Conclusions

 

A time-dependent and reversible serous retinopathy can develop in CM patients and UM patients treated with binimetinib or a combination of binimetinib and sotrastaurin. A minority of patients develop visual complaints, which are generally mild and transient. A possible cause of binimetinib-associated serous retinopathy may be toxicity of study medication, but autoantibodies can also be involved.