The Journal of the Arkansas Medical Society Med Journal June 2020 | Page 18

Case Study
by Kyle A. Kirkland, DO 1 , Sunali Goyal, MD 1
Abstract
Purpose: To describe of retinal pigment epithelium
detachment (PED) and keratoconjunctivitis
sicca (KCS) in a patient treated with nivolumab,
an anti-programmed death-1 inhibitor (PD-1) antibody.
Methods: Case report of a patient referred by oncology
for severe eye irritation and blurry vision
while undergoing nivolumab therapy for metastatic
cutaneous melanoma.
Conclusion: This is the first described case
of PED in a patient on nivolumab therapy. Although
KCS is readily reported in the literature,
aggressive and early treatment can completely
resolve ocular surface disease. Drugs in the
anti-PD-1 family require extremely aggressive
treatment for ocular surface disease, and we suggest
screening for potential retinal involvement.
Introduction
Retinal pigment epithelium detachment (PED) is
the separation of the retinal pigment epithelium
(RPE) from Bruch’s membrane. Pigment epithelial
detachment is a prominent feature in retinal
diseases such as age-related macular degeneration
(AMD). 1 Here we describe a case with an
apparent association between nivolumab, a treatment
option for metastatic melanoma, and PED.
Nivolumab is an anti-programmed cell death protein-1
(anti-PD-1) monoclonal antibody that inhibits
T-cell check points that normally allow tumor
cells to evade the host’s immunity. 2-4 Several
published cases have reported the association of
ocular surface disease (OSD) with use of nivolumab.
2-6 Herein, we present a case of PED associated
with nivolumab for metastatic melanoma.
Case
A 59-year-old male with metastatic cutaneous
melanoma on treatment with nivolumab was
referred to the ophthalmology clinic for bilateral
red, painful eyes for about one month with noticeably
decreased vision over two weeks. At the
time of referral, the patient was undergoing his
tenth cycle of nivolumab therapy. He denied any
history of dry eye disease. On initial evaluation,
the patient had best corrected visual acuity of
20/200 in both eyes. Ocular examination revealed
dense punctate epithelial erosions with epithelial
edema, diffuse conjunctival staining, and severe
papillary reaction in both eyes. Dilated fundus
examination revealed a dome-shaped elevation
in the right macula. High-definition ocular coherence
tomography (HD-OCT) was then performed,
which revealed right perifoveal PED. (Figures
A-D) The patient was started on cyclosporine
0.05% with preservative-free-artificial tears every
two hours while awake and lubricating ointment
three times daily for severe keratitis. The PED was
managed with observation. Subsequent visits at
one-month and three-month follow-up showed
1
Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, Ark.
Program Death-1 Inhibitor-Induced Pigment Epithelial
Detachment and Keratoconjunctivitis Sicca
Figures A-D. A-B, Severe keratoconjunctivitis sicca in right and left eyes, respectively,
showing dense fluorescein dye uptake centrally with some lid margin
staining on the right eye. Figure C, High-definition optical coherence tomography
(HD-OCT) highlighting a perifoveal pigment epithelial detachment (PED) [arrow].
Figure D, HD-OCT showing resolution of PED.
some improvement in corneal surface with mild
improvement in symptoms. The PED remained
stable. Due to persistent epitheliopathy, autologous
serum tears were initiated for OSD and continued
observation for the PED was again elected.
Three months of serum tears resulted in tremendous
improvement in signs and symptoms and
the patient’s uncorrected visual acuity increased
to 20/25 OU. Meanwhile, after his twelfth round
of nivolumab, oncology recommended stopping
therapy due to systemic adverse effects
and opted for serial imaging and dermatologic
exams. At his next follow-up appointment of
six months, the patient maintained stable vision
with resolution of all signs and symptoms
of ocular surface disease. Ocular coherence tomography
of the macula showed nearly 50% reduction
in PED in size after stopping nivolumab.
282 • The Journal of the Arkansas Medical Society www.ArkMed.org