MEK inhibitor-associated central retinal vein occlusion associated with hyperhomocysteinemia and MTHFR variants Journal Article


Authors: Francis, J. H.; Diamond, E. L.; Chi, P.; Jaben, K.; Hyman, D. M.; Abramson, D. H.
Article Title: MEK inhibitor-associated central retinal vein occlusion associated with hyperhomocysteinemia and MTHFR variants
Abstract: 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, retrospective cohort study (between December 2006 and September 2018). Three of 546 patients enrolled in 46 prospective trials involving treatment with MEK inhibitors at Memorial Sloan Kettering Cancer Center were identified as having CRVO. Clinical examination and course, multimodal ophthalmic imaging, and serum laboratory results (including homocysteine levels and genetic variants of methylene tetrahydrofolate reductase [MTHFR]) were reviewed for the 3 affected patients. All 3 patients with MEK inhibitor-associated CRVO had elevated serum homocysteine and gene variants of MTHFR (1 homozygous for A1298C, 1 heterozygous for A1298C, and 1 homozygous for C677T). Following intravitreous injections of anti-VEGF and discontinuation of drug, all patients regained vision to their baseline. Discussion: MEK 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. © 2019 S. Karger AG, Basel. Copyright: All rights reserved.
Keywords: adult; clinical article; middle aged; case report; drug dose reduction; drug withdrawal; side effect; unspecified side effect; gastrointestinal stromal tumor; imatinib; disease association; ovary cancer; cohort analysis; genetic variability; heterozygote; retrospective study; rash; acne; aflibercept; homozygote; creatine kinase; homocysteine; amino acid blood level; visual impairment; cardiomyopathy; creatine kinase blood level; optical coherence tomography; 5,10 methylenetetrahydrofolate reductase (fadh2); retina macula cystoid edema; heart ejection fraction; mitogen activated protein kinase kinase inhibitor; hyperhomocysteinemia; heart ventricle failure; human; male; female; priority journal; article; erdheim chester disease; fluorescence angiography; central retina vein occlusion
Journal Title: Ocular Oncology and Pathology
Volume: 6
Issue: 3
ISSN: 2296-4681
Publisher: Karger  
Date Published: 2020-05-01
Start Page: 159
End Page: 163
Language: English
DOI: 10.1159/000501155
PROVIDER: scopus
PMCID: PMC7250324
PUBMED: 32509759
DOI/URL:
Notes: Article -- Export Date: 1 June 2020 -- Source: Scopus
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MSK Authors
  1. Jasmine Helen Francis
    221 Francis
  2. David H Abramson
    364 Abramson
  3. Ping Chi
    153 Chi
  4. David Hyman
    352 Hyman
  5. Eli Louis Diamond
    172 Diamond
  6. Korey A. Jaben
    7 Jaben