Bilateral Visual Field Defects in a Patient Treated With the Mek and Braf Inhibitors Trametinib and Dabrafenib for Melanoma of Unknown Origin

Abstract

In addition to the widely known class-related retinal toxicity, MEK and BRAF inhibitor-associated adverse events may also involve the optic nerve head, causing visual field defects probably regressing spontaneously after discontinuation of targeted oncologic therapy. In such cases, repeat brain imaging and exclusion of melanoma-associated retinopathy is recommended. Reinitiation of treatment and subsequent dose escalation seem to be feasible, but should be monitored by an ophthalmologist.

Retinal Vein Occlusion in a Patient on Dabrafenib and Trametinib Therapy for Metastatic Melanoma

“…Other adverse ophthalmological events described were eyelid edema [ 1 ], uveitis (1-10%) [ 4 ], central serous chorioretinopathy (2%) [ 5 ], retinal detachment [ 2 , 6 ], and even visual field loss [ 7 ]. Retinal vein occlusion, which was diagnosed in our patient, is rare.…”

“…The mechanism by which venous occlusion occurs is suggested to be associated with the inhibition of the MAPK pathway by dabrafenib and trametinib, which would generate alterations in the blood-retinal barrier and prothrombotic effects, secondary to the effect of reactive oxygen species and of the dysfunction in the inflammation process produced by them [6][7][8][9]. According to some authors like Farooq and Mangla, this adverse event could be potentially avoided if a checkpoint inhibitor was used.…”

“…The combination of therapies with BRAF inhibitors (dabrafenib) and MEK inhibitors (trametinib) has been shown to improve survival in patients with advanced melanomas with the BRAF V600 mutation (E and K) and to decrease the risk of recurrence [1]. Even though these are generally considered safe drugs, many authors have reported certain adverse effects in recent years, both systemic and ophthalmological [2][3][4][5][6][7].…”

The Impact of Systemic Medications on Retinal Function

“…Full-field ERG might also be decreased and improved with dose reduction 156. Automated perimetry may help detect reversible visual field defects in patients with optic neuropathy 97…”

“…Brownish discoloration of conjunctiva, thin superficial lines in the cornea, and tearing may occur 97,98. The visual acuity may be mildly impacted as well.…”