Correspondence
1. Tobacco and Genetics Consortium. Genome-wide meta-
analyses identify multiple loci associated with smoking behavior.
Nat Genet 2010;42:441-7.
2. Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and
setting national goals for cardiovascular health promotion and
Selumetinib in Plexiform Neurofibromas
To the Editor: Dombi et al. (Dec. 29 issue)1 de-
scribe the successful use of a mitogen-activated
protein kinase (MAPK) kinase (MEK) inhibitor,
selumetinib, in 24 children with neurofibroma-
tosis type 1. They performed eye examinations in
these children and found only 1 patient who had
a cataract and no other ophthalmic toxic effect.
In adult patients who use MEK inhibitors, we and
others have observed a very high rate (approach-
ing 80%) of serous detachments when careful
ophthalmologic examination was combined with
optical coherence tomography (OCT).2 This class
effect has been described with every MEK in-
hibitor that has been used clinically, including in
2 children.3 Therefore, we wish to know whether
careful OCT evaluation was done in this study
and, if so, why the authors think that there was
such a difference from previous studies in which
MEK inhibitors were used. We believe that if fur-
ther long-term use of MEK inhibitors is contem-
plated in this population, careful trials with the
use of periodic OCT monitoring are warranted.
JoseS. Pulido, M.D.
Mayo Clinic
Rochester, MN
pulido.jose@mayo.edu prospective clinical trials are needed to define
JeffreyS. Heier, M.D.
Ophthalmic Consultants of Boston
Boston, MA
AlanD. Marmorstein, Ph.D.
Mayo Clinic
Rochester, MN
No potential conflict of interest relevant to this letter was re-
ported.
1. Dombi E, Baldwin A, Marcus LJ, et al. Activity of selumetinib
in neurofibromatosis type 1related plexiform neurofibromas.
N Engl J Med 2016;375:2550-60.
2. Weber ML, Liang MC, Flaherty KT, Heier JS. Subretinal fluid
associated with MEK inhibitor use in the treatment of systemic
cancer. JAMA Ophthalmol 2016;134:855-62.
3. Avery RA, Trimboli-Heidler C, Kilburn LB. Separation of
outer retinal layers secondary to selumetinib. J AAPOS 2016;20:
268-71.
DOI: 10.1056/NEJMc1701029
n engl j med 376;12nejm.org March 23, 2017
The New England Journal of Medicine
Downloaded from nejm.org on March 31, 2017. For personal use only. No other uses without permission.
Copyright 2017 Massachusetts Medical Society. All rights reserved.
disease reduction: the American Heart Associations strategic
Impact Goal through 2020 and beyond. Circulation 2010;121:
586-613.
DOI: 10.1056/NEJMc1700362
The author and colleagues reply: OCT was
performed regularly in all 15 study patients who
were enrolled at the National Cancer Institute.
All 126 OCT scans (median, 8 per patient) were
normal except for 1 that, on retrospective review,
showed a subtle separation in the outer retinal
layer of both eyes. This 17-year-old patient had
normal vision and had had normal results on
9previous OCT scans. Repeat OCT during selu-
metinib treatment 6 months later showed resolu-
tion of the abnormalities.
We can only speculate about why the children
in our study had a very low incidence of ophthal-
mic toxic effects. Our patients received selu-
metinib at lower doses than are used in adults
(48 to 72% of the recommended dose in adults),
which could be responsible. In addition, the inci-
dence of ophthalmic toxic effects may vary among
MEK inhibitors.
We are unaware of pediatric patients whose
asymptomatic retinal changes on OCT resulted
in clinically significant toxic effects. It is impor-
tant for all patients receiving MEK inhibitors to
be followed closely with serial ophthalmologic
evaluations. We agree with Pulido et al. that
the usefulness of OCT in monitoring and under-
standing potential ocular toxic effects of MEK
inhibitors in children.
Andrea Gross, M.D.
Childrens National Medical Center
Washington, DC
Rachel Bishop, M.D.
National Eye Institute
Bethesda, MD
BrigitteC. Widemann, M.D.
National Cancer Institute
Bethesda, MD
widemanb@mail.nih.gov
Drs. Gross and Bishop report no potential conflict of interest
relevant to this letter. Since publication of her article, Dr. Wide-
mann reports no further potential conflict of interest.
DOI: 10.1056/NEJMc1701029
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