Subretinal Fluid Associated With MEK Inhibitor Use in the Treatment of Systemic Cancer.
OBJECTIVE
The use of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors has become more common in the treatment of systemic cancer. These agents have been associated with a central serous-like retinopathy in some patients. Recognition of such retinal findings and the relatively benign nature of these events is important to avoid unnecessary intervention, including the cessation of a potentially life-prolonging medication.


OBJECTIVE
To evaluate the presence and characteristics of subretinal fluid (SRF) associated with the use of MEK inhibitors in the treatment of systemic cancer and to correlate the presence of SRF with visual acuity and symptoms over time.


METHODS
Post hoc analysis was conducted of prospectively collected data from 51 patients with locally advanced or metastatic cancer undergoing treatment with the MEK inhibitor binimetinib in 1 of 4 clinical trials. All clinical trial participants underwent complete ophthalmic examination by retina specialists at a private practice in Boston, Massachusetts, and were monitored between February 29, 2012, and January 8, 2014. The examination included Snellen-measured visual acuity, dilated fundus examination, and spectral-domain optical coherence tomography at baseline, biweekly for 2 months, then monthly for the remainder of their trial participation. Post hoc design and data analysis were performed between December 1, 2013, and June 20, 2014.


METHODS
Visual symptoms, visual acuity, fundus appearance, and the presence and characteristics of SRF noted on optical coherence tomography. The characteristics of angiograms performed at the discretion of the treating physician were reviewed.


RESULTS
Of the 51 participants, 18 (35%) were men; the mean (SD) age was 60 (13) years (range, 32-87 years). Forty-six (90%) study participants developed SRF during the study period, with 9 (20%) experiencing symptoms at any point. The mean (SD) central retinal thickness of 39 study participants who developed SRF at the first visit increased from 280 (26) µm at baseline to 316 (43) µm at the first visit after starting binimetinib treatment (paired t test, P < .001). On examination, SRF appeared as elevated, yellow-orange pockets in the fovea and/or along the arcades. Corresponding optical coherence tomographic imaging revealed SRF beneath the interdigitation zone. The fovea was affected in 37 of 46 (80%) individuals; the location of SRF accumulation varied. Visual symptoms were mild and mainly transient, occurring in 9 participants with SRF (20%; 95% CI, 10%-33%). Only 2 participants (4%) were found to have SRF at the last study visit after discontinuation of treatment with binimetinib. Both had Snellen-measured visual acuity of 20/25 or better.


CONCLUSIONS
The presence of SRF was common in study participants undergoing treatment with the MEK inhibitor binimetinib. Visual symptoms were mild and mainly transient. The presence of SRF did not lead to permanent ocular sequelae. Cessation of life-extending treatment with MEK inhibitors is not indicated when SRF is present.
Ophthalmic Consultants of Boston, Boston, Massachusetts2Ophthalmology Service, Walter Reed National Military Medical Center, Bethesda, Maryland.
Marissa L
ML
Weber
Ophthalmic Consultants of Boston, Boston, Massachusetts3New England Eye Center, Tufts Medical Center, Boston, Massachusetts.
Michelle C
MC
Liang
Department of Medicine, Massachusetts General Hospital, Boston.
Keith T
KT
Flaherty
Ophthalmic Consultants of Boston, Boston, Massachusetts.
Jeffrey S
JS
Heier
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D056833:Central Serous Chorioretinopathy / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D011446:Prospective Studies; D058471:Subretinal Fluid / Q000378:metabolism*; D041623:Tomography, Optical Coherence / Q000379:methods*; D014792:Visual Acuity
D000970:Antineoplastic Agents; D001562:Benzimidazoles; C581313:binimetinib; D048369:MAP Kinase Kinase 1