Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma

Elon H C Van Dijk, Carla M L Van Herpen, Marina Marinkovic, John B A G Haanen, Drake Amundson, Gré P M Luyten, Martine J. Jager, Ellen H W Kapiteijn, Jan E E Keunen, Grazyna Adamus, Camiel J F Boon

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Abstract

Purpose To analyze the clinical characteristics of a serous retinopathy associated with mitogen-activated protein kinase kinase (MEK) inhibition with binimetinib treatment for metastatic cutaneous melanoma (CM) and uveal melanoma (UM), and to determine possible pathogenetic mechanisms that may lead to this retinopathy. Design Prospective observational, cohort-based, cross-sectional study. Participants Thirty CM patients and 5 UM patients treated with the MEK inhibitor binimetinib (CM) or a combination of binimetinib and the protein kinase C inhibitor sotrastaurin (UM). Methods Extensive ophthalmic examination was performed, including Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, applanation tonometry, slit-lamp examination, indirect ophthalmoscopy, digital color fundus photography, and optical coherence tomography (OCT). In selected cases, additional examinations were performed, including visual field testing and electro-oculography (EOG). Blood samples were obtained from 3 CM patients and 3 UM patients to analyze the presence of autoantibodies against retinal and retinal pigment epithelium (RPE) proteins. Main Outcome Measures Visual symptoms, visual acuity, fundus appearance, characteristics on OCT, fundus autofluorescence (FAF), and EOG. Results Six CM patients (20%) and 2 UM patients (40%) reported visual symptoms during the study. The median time to the onset of symptoms, which were all mild and transient, was 3.5 days (range,

Original languageEnglish (US)
Pages (from-to)1907-1916
Number of pages10
JournalOphthalmology
Volume122
Issue number9
DOIs
StatePublished - Sep 1 2015

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Mitogen-Activated Protein Kinase Kinases
Melanoma
Skin
Optical Coherence Tomography
Visual Acuity
Ophthalmoscopy
Retinal Pigment Epithelium
Protein C Inhibitor
Photography
Manometry
Diabetic Retinopathy
Protein Kinase Inhibitors
Visual Fields
Autoantibodies
Protein Kinase C
MEK162
Inhibition (Psychology)
Uveal melanoma
Color
Cross-Sectional Studies

ASJC Scopus subject areas

  • Ophthalmology
  • Medicine(all)

Cite this

Van Dijk, E. H. C., Van Herpen, C. M. L., Marinkovic, M., Haanen, J. B. A. G., Amundson, D., Luyten, G. P. M., ... Boon, C. J. F. (2015). Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma. Ophthalmology, 122(9), 1907-1916. https://doi.org/10.1016/j.ophtha.2015.05.027

Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma. / Van Dijk, Elon H C; Van Herpen, Carla M L; Marinkovic, Marina; Haanen, John B A G; Amundson, Drake; Luyten, Gré P M; Jager, Martine J.; Kapiteijn, Ellen H W; Keunen, Jan E E; Adamus, Grazyna; Boon, Camiel J F.

In: Ophthalmology, Vol. 122, No. 9, 01.09.2015, p. 1907-1916.

Research output: Contribution to journalArticle

Van Dijk, EHC, Van Herpen, CML, Marinkovic, M, Haanen, JBAG, Amundson, D, Luyten, GPM, Jager, MJ, Kapiteijn, EHW, Keunen, JEE, Adamus, G & Boon, CJF 2015, 'Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma', Ophthalmology, vol. 122, no. 9, pp. 1907-1916. https://doi.org/10.1016/j.ophtha.2015.05.027
Van Dijk, Elon H C ; Van Herpen, Carla M L ; Marinkovic, Marina ; Haanen, John B A G ; Amundson, Drake ; Luyten, Gré P M ; Jager, Martine J. ; Kapiteijn, Ellen H W ; Keunen, Jan E E ; Adamus, Grazyna ; Boon, Camiel J F. / Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma. In: Ophthalmology. 2015 ; Vol. 122, No. 9. pp. 1907-1916.
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abstract = "Purpose To analyze the clinical characteristics of a serous retinopathy associated with mitogen-activated protein kinase kinase (MEK) inhibition with binimetinib treatment for metastatic cutaneous melanoma (CM) and uveal melanoma (UM), and to determine possible pathogenetic mechanisms that may lead to this retinopathy. Design Prospective observational, cohort-based, cross-sectional study. Participants Thirty CM patients and 5 UM patients treated with the MEK inhibitor binimetinib (CM) or a combination of binimetinib and the protein kinase C inhibitor sotrastaurin (UM). Methods Extensive ophthalmic examination was performed, including Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, applanation tonometry, slit-lamp examination, indirect ophthalmoscopy, digital color fundus photography, and optical coherence tomography (OCT). In selected cases, additional examinations were performed, including visual field testing and electro-oculography (EOG). Blood samples were obtained from 3 CM patients and 3 UM patients to analyze the presence of autoantibodies against retinal and retinal pigment epithelium (RPE) proteins. Main Outcome Measures Visual symptoms, visual acuity, fundus appearance, characteristics on OCT, fundus autofluorescence (FAF), and EOG. Results Six CM patients (20{\%}) and 2 UM patients (40{\%}) reported visual symptoms during the study. The median time to the onset of symptoms, which were all mild and transient, was 3.5 days (range,",
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