The Journal of the Arkansas Medical Society Med Journal June 2020 | Page 19

Discussion
The advent of new drugs to harness the ability
of one’s immune system to treat cancer has led
to promising results, specifically for metastatic
melanoma. Programmed death 1 (PD-1) protein
is a T-cell inhibitory receptor that allows circumvention
of the body’s natural T-cell immunity.
Programmed death ligand 1 (PD-L1) is the primary
ligand that is upregulated in solid tumors
that propagates this circumvention. Nivolumab
binds the PD-1 receptor and disrupts the inhibitory
pathway, allowing for T-cell upregulation
and, thereby, tumor regression. 2-4 Nivolumab
has been reported to cause bilateral uveitis with
keratitis5 and corneal perforation secondary to
OSD.6 However, to the best of our knowledge,
PED in association with nivolumab has not been
described previously.
In a multicenter phase 1 trial of 207 patients treated
with nivolumab, 5% of patients were reported
to have dry eye .2 Zimmer et al 3 report 1.6% of patients
with ocular adverse events including uveitis
with macular edema while using a similar anti-PD-1
drug. The OSD associated with anti-PD-1
therapy is readily documented. In our case, the
patient had only minimal response to cyclosporine
0.5% and had significant relief once autologous
serum tears were initiated. In combination
with the halting of immunotherapy, the patient
had complete resolution of the OSD. Although
the patient did not have an OCT showing the
lack of a PED, there was spontaneous reduction
in size soon after discontinuation of nivolumab.
Fortunately for our patient, the lesion is not problematic
visually, but a PED involving the fovea
can be visually significant. Our case reiterates the
need for aggressive treatment for OSD in patients
taking nivolumab with either cyclosporine 0.5%
or autologous serum tears. It also highlights the
importance of complete evaluation of the eye as
there may be an association of retinal pathology
in patients receiving anti-PD-1 therapy.
References
1. Zayit-Soudry S, Moroz I, Loewenstein A.
Retinal pigment epithelial detachment. Surv
Ophthalmol. 2007;52(3):227-243.
2. Brahmer JR, Tykodi SS, Chow LQ, et al.
Safety and activity of anti-PD-L1 antibody
in patients with advanced cancer. N Engl J
Med. 2012;366(26):2455-2465.
3. Zimmer L, Goldinger SM, Hofmann L, et al.
Neurological, respiratory, musculoskeletal,
cardiac and ocular side-effects of anti-PD-1
therapy. Eur J Cancer. 2016;60:210-225.
4. Cappelli LC, Gutierrez AK, Baer AN, et al.
Inflammatory arthritis and sicca syndrome
induced by nivolumab and ipilimumab. Ann
Rheum Dis. 2017;76(1):43-50.
5. Baughman DM, Lee CS, Snydsman BE,
Jung HC. Bilateral Uveitis and Keratitis Following
Nivolumab Treatment for Metastatic
Melanoma. Med Case Rep (Wilmington).
2017;3(2).
6. Nguyen AT, Elia M, Materin MA, Sznol
M, Chow J. Cyclosporine for Dry Eye Associated
With Nivolumab: A Case Progressing
to Corneal Perforation. Cornea.
2016;35(3):399-401.
Be a Resource for Your
State Legislators
At this unprecedented time, it seems everyone is looking for medical guidance, answers
and advice. Members of the Arkansas Legislature are doing their best to field questions
from constituents regarding the current situation. AMS encourages you to share your
knowledge and insight with your legislators.
If interested, click on the link below to find your state Representative and Senator, then
contact them offering yourself as a medical resource to answer any questions they might
have. We are all in this together.
https://www.arkmed.org/advocacy/locate-your-legislator/
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Volume 116 • Number 12 JUNE 2020 • 283