MEK Inhibitor-Associated Central Retinal Vein Occlusion Associated with Hyperhomocysteinemia and MTHFR Variants

Abstract

Central retinal vein occlusion (CRVO) is a rare side effect of MEK inhibitors. • MEK inhibitor-associated CRVO may result in permanent drug discontinuation. Novel Insights• MEK inhibitor-associated CRVO may be associated with hyperhomocysteinemia, suggesting a potential role for hyperhomocysteinemia screening prior to initiation of MEK inhibitor therapy. • In this small cohort, MEK inhibitor-associated CRVO was associated with good visual recovery following intravitreous anti-VEGF. AbstractBackground: Central retinal vein occlusion (CRVO) is a visually threatening event that has rarely been observed in patients taking MEK1/2 inhibitors and that may necessitate permanent discontinuation of a potentially efficacious therapy. We investigated the clinical characteristics of CRVO in patients on mitogen-activated protein kinase kinase (MEK) inhibition to better understand their predisposing factors and clinical course. Case Series: This was a single-center, ret-inhibitor-associated CRVO is a rare event which can exhibit visual recovery after drug cessation and intravitreous anti-VEGF injections. In this cohort, it was associated with hyperhomocysteinemia and genetic mutations in MTHFR, suggesting a potential role for hyperhomocysteinemia screening prior to initiation of MEK inhibitor therapy.

Phase Ib Trial of the Combination of Imatinib and Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumors

“…The dropped head syndrome and CRVO are class effects of MEK inhibitors and are typically reversable with complete resolution of symptoms through dose reduction or discontinuation of drugs and appropriate medical management (22)(23)(24). The MEK inhibitor-associated CRVO has been observed to associate with hyperhomocysteinemia and MTHFR variants (22). There was no clinically significant grade 4 or grade 5 AEs at least possibly associated with study medications in this trial.…”

“…One patient developed a grade 3 central retinal vein occlusion (CRVO) requiring discontinuation of study drug and intravitreal bevacizumab injection of the affected eye with subsequent full recovery of vision. The dropped head syndrome and CRVO are class effects of MEK inhibitors and are typically reversable with complete resolution of symptoms through dose reduction or discontinuation of drugs and appropriate medical management (22)(23)(24). The MEK inhibitor-associated CRVO has been observed to associate with hyperhomocysteinemia and MTHFR variants (22).…”

Re: Magone et al.: Ocular adverse effects of infigratinib, a new fibroblast growth factor receptor tyrosine kinase inhibitor (Ophthalmology. 2021;128:624–626)

“…2 In our experience, the fluid foci in patients with MEK inhibitoreassociated retinopathy or FGFR inhibitoreassociated retinopathy occurs between the RPE and interdigitation zone of the neurosensory retina. 3,4 This is one of the key features that helps to differentiate these findings from central serous chorioretinopathy. 3 Unfortunately, many of the early descriptions of the retinal findings associated with MEK and FGFR inhibitors were incorrectly termed central serous chorioretinopathy and propagation of this description is confusing.…”

“…3,4 This is one of the key features that helps to differentiate these findings from central serous chorioretinopathy. 3 Unfortunately, many of the early descriptions of the retinal findings associated with MEK and FGFR inhibitors were incorrectly termed central serous chorioretinopathy and propagation of this description is confusing. 3 The importance of carefully distinguishing these 2 entities is clinically important, as is the absence of recurrence with drug rechallenge.…”

“…3 Unfortunately, many of the early descriptions of the retinal findings associated with MEK and FGFR inhibitors were incorrectly termed central serous chorioretinopathy and propagation of this description is confusing. 3 The importance of carefully distinguishing these 2 entities is clinically important, as is the absence of recurrence with drug rechallenge. The neurosensory detachments associated with MEK and FGFR inhibitors are typically self-limited, without residual effects on the eye or vision, and can be observed while patients remain on the drug.…”