Oxaliplatin-associated amaurosis fugax has not been reported, and its clinical course and treatment remain largely unclear. A 70-year-old man with advanced gastric cancer was treated with the SOX regimen. After cycle 1 of oxaliplatin infusion, the patient realized that his right eye had visual field impairment, which he described as darkening of the right half of his visual field and loss of vision lasting about 1 min and occurring about 7 times a day. The daily frequency of this occurrence gradually decreased, and his visual field impairment improved in 1 week. However, as the same symptoms recurred from cycle 2 to cycle 5 of treatment, oxaliplatin was discontinued from cycle 6 and switched to S-1 monotherapy. Subsequently, the patient’s amaurosis fugax improved. To our knowledge, this is the first report describing clinical course and treatment of oxaliplatin-associated amaurosis fugax

Kimitoshi Kubo

Masayuki Higashino

Momoko Tsuda

Mototsugu Kato

Noriko Kimura

Ryosuke Watanabe

Case Reports in Oncology

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© 2021 The Author(s).
Published by S. Karger AG, Basel
Case Report
Case Rep Oncol 2021;14:832–837
Oxaliplatin-Associated Amaurosis 
Fugax
Kimitoshi Kubo a    Noriko Kimura b    Ryosuke Watanabe a    
Masayuki Higashino a    Momoko Tsuda a    Mototsugu Kato a
aDepartment of Gastroenterology, National Hospital Organization Hakodate National 
Hospital, Hakodate, Japan; bDepartment of Pathology, National Hospital Organization 
Hakodate National Hospital, Hakodate, Japan
Keywords
Oxaliplatin · S-1 + oxaliplatin · Amaurosis fugax · Ocular toxicity
Abstract
Oxaliplatin-associated amaurosis fugax has not been reported, and its clinical course and 
treatment remain largely unclear. A 70-year-old man with advanced gastric cancer was treat-
ed with the SOX regimen. After cycle 1 of oxaliplatin infusion, the patient realized that his right 
eye had visual field impairment, which he described as darkening of the right half of his vi-
sual field and loss of vision lasting about 1 min and occurring about 7 times a day. The daily 
frequency of this occurrence gradually decreased, and his visual field impairment improved 
in 1 week. However, as the same symptoms recurred from cycle 2 to cycle 5 of treatment, ox-
aliplatin was discontinued from cycle 6 and switched to S-1 monotherapy. Subsequently, the 
patient’s amaurosis fugax improved. To our knowledge, this is the first report describing clin-
ical course and treatment of oxaliplatin-associated amaurosis fugax.
© 2021 The Author(s).
Published by S. Karger AG, Basel
Introduction
Oxaliplatin, a third-generation platinum analog, is widely used in the treatment of various 
cancers including colorectal and gastric cancers [1, 2]. While the most common adverse 
effects associated with oxaliplatin are neurotoxicity (acute, chromic, and persistent) and 
delayed hypersensitivity reactions [3], and ocular toxicity has been reported as an infrequent 
adverse event associated with oxaliplatin [4]. We herein report a case of oxaliplatin-asso-
ciated amaurosis fugax.
Received: March 16, 2021
Accepted: March 30, 2021
Published online: June 11, 2021
Correspondence to: 
Kimitoshi Kubo, kubotti25 @ yahoo.co.jp
www.karger.com/cro
This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 Interna tional License 
(CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial 
purposes requires written permission.
DOI: 10.1159/000516271
833Case Rep Oncol 2021;14:832–837
Kubo et al.: Amaurosis Fugax
www.karger.com/cro
© 2021 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000516271
Case Report/Case Presentation
A 70-year-old man who complained of nausea, vomiting, and weight loss was referred to 
our hospital for examination and treatment. He had a history of hyperthyroidism, diabetes, 
hypertension, osteoporosis, infectious uveitis, and retinal detachment. Computed tomog-
raphy revealed thickening of the gastric wall from the gastric body to the prepyloric region, 
as well as retention of food residues (Fig. 1). Esophagogastroduodenoscopy revealed friable 
and irregular mucosa, and a depressed lesion extending from the gastric antrum to the lower 
body (Fig. 2a). An esophagogastroduodenoscopy biopsy revealed poorly differentiated 
adenocarcinoma (por) (Fig. 2b). Surgery was performed for preoperative diagnosis of undif-
ferentiated advanced gastric cancer. Total gastrectomy was initially planned but then was 
abandoned during the operation in favor of gastrojejunostomy because of a strong adhesion 
to the head of the pancreas. Systemic chemotherapy with the SOX regimen (S-1, 120 mg/day 
on days 1–14; oxaliplatin, 170 mg on day 1) was initiated as treatment because the patient 
tested HER2-negative in immunohistochemical staining.
After cycle 1 of oxaliplatin infusion, the patient realized that his right eye had visual field 
impairment, which he described as darkening of the right half of his visual field and loss of 
vision lasting about 1 min and occurring about 7 times a day. The daily frequency of this 
occurrence gradually decreased, and his visual field impairment improved in 1 week. No 
visual field impairment occurred in the left eye. Since the same symptoms recurred from the 
second to the fifth cycle of treatment, we consulted with an ophthalmologist. An ophthalmologic 
Fig. 2. Endoscopic findings and a histopathological examination of the biopsy specimens. a EGD revealed fri-
able and irregular mucosa, and a depressed lesion extending from the gastric antrum to the lower body. 
b Histopathological examination of biopsy specimens showed poorly differentiated adenocarcinoma (por) 
(×400) (scale bar, 50 μm). EGD, esophagogastroduodenoscopy.
a b
Fig. 1. CT findings. CT revealed thickening of 
the gastric wall from the gastric body to the 
prepyloric region as well as retention of food 
residues. CT, computed tomography.
834Case Rep Oncol 2021;14:832–837
Kubo et al.: Amaurosis Fugax
www.karger.com/cro
© 2021 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000516271
examination revealed no obvious damage to the retinal and optic nerves. The patient showed 
no abnormal findings in the brain or around the orbit on magnetic resonance imaging (MRI) 
(Fig. 3a, b), no stenosis or aneurysm in the internal carotid artery or ophthalmic artery on 
3D-MRI (Fig. 3c), and no plaque or stenotic lesion in the bilateral carotid arteries on carotid 
artery ultrasound. Thus, the ophthalmologist arrived at the diagnosis of amaurosis fugax, but 
without mentioning its cause or recommending any specific treatment. His clinical course led 
us to suspect oxaliplatin-associated amaurosis fugax and to discontinue oxaliplatin and 
switch to S-1 monotherapy from cycle 6. Subsequently, the patient’s amaurosis fugax 
improved.
After an improvement shown after cycle 6 in gastric wall thickening on computed tomog-
raphy, total gastrectomy was performed with D2 lymph node dissection. The gastric lesion in 
the patient was diagnosed as tubular adenocarcinoma, well-differentiated type (tub1 > tub2), 
45 × 13 mm, ypT3 (SS), ly0, v1, N0, M0, grade 1b, stage IIA. The patient underwent adjuvant 
chemotherapy with S-1 and has shown no recurrence for 6 months. In addition, no visual field 
impairment occurred since.
Discussion/Conclusion
Our case has 2 important clinical implications. First, amaurosis fugax may occur as an 
adverse event associated with oxaliplatin, while the clinical course and treatment of amau-
rosis fugax associated with oxaliplatin remain largely unclear, with no reports available in the 
literature.
Given that ocular toxicity associated with cancer chemotherapy has a great impact on 
quality of life, its timely recognition contributes to better patient management [5]. A study of 
oxaliplatin-associated neurotoxicity using an interview-based questionnaire reported 
blurred vision, ptosis, eye pain, and visual field cuts in 10–15% of all specific symptoms [6]. 
To date, 9 cases of oxaliplatin-associated ocular toxicity have been reported (males/females, 
3/6; mean age, 56.9 years) (Table 1) [7–11]. Ocular toxicities included visual field impairment 
(n = 6) (tunnel vision, 3; visual loss in the lower half of visual field, 1; visual loss from the 
peripheral to central visual field, 1; and blurred vision, 1) and blepharoptosis (n = 3). Ocular 
symptoms are reported to have improved in all patients with the following treatments: oxali-
platin discontinuation (n = 7), prolonged oxaliplatin administration time (n = 1), and sponta-
neous improvement (n = 1). In the present case, visual field impairment affecting the right 
half of the right eye occurred after administration of oxaliplatin and improved after its discon-
tinuation. In addition, visual field impairment did not recur after S-1 monotherapy. Therefore, 
Fig. 3. MRI findings. a, b MRI showed no abnormal findings in the brain or around the orbit. c 3D-MRI showed 
no stenosis or aneurysm in the internal carotid artery or ophthalmic artery. MRI, magnetic resonance imaging.
a b c
835Case Rep Oncol 2021;14:832–837
Kubo et al.: Amaurosis Fugax
www.karger.com/cro
© 2021 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000516271
Ta
bl
e 
1.
 C
as
es
 re
po
rt
ed
 to
 d
at
e 
of
 o
xa
lip
la
tin
-a
ss
oc
ia
te
d 
oc
ul
ar
 to
xi
ci
tie
s
N
o.
Re
f.
Ye
ar
Ag
e,
 y
ea
rs
Se
x
Re
gi
m
en
Cy
cl
e*
Oc
ul
ar
 to
xi
ci
ty
Tr
ea
tm
en
t
1
[7
]
20
06
45
F
FO
LF
OX
3
Vi
su
al
 lo
ss
 a
ffe
ct
in
g 
th
e 
pe
ri
ph
er
al
 to
  
ce
nt
ra
l v
is
ua
l f
ie
ld
Ox
al
ip
la
tin
 w
as
 d
is
co
nt
in
ue
d.
 A
fte
r 4
 m
on
th
s, 
oc
ul
ar
 to
xi
ci
ty
  
im
pr
ov
ed
 a
nd
 o
xa
lip
la
tin
 w
as
 re
st
ar
te
d.
 T
he
re
 w
as
 n
o 
 
re
cu
rr
en
ce
 o
f t
he
 sy
m
pt
om
2
57
M
FO
LF
OX
1
Tu
nn
el
 v
is
io
n
Ox
al
ip
la
tin
 w
as
 d
is
co
nt
in
ue
d 
fr
om
 cy
cl
e 
4,
 a
nd
 th
e 
sy
m
pt
om
  
im
pr
ov
ed
3
52
M
Ox
al
ip
la
tin
  
m
on
ot
he
ra
py
2
Tu
nn
el
 v
is
io
n
Ox
al
ip
la
tin
 w
as
 d
is
co
nt
in
ue
d,
 a
nd
 th
e 
re
gi
m
en
 ch
an
ge
d,
  
an
d 
th
e 
sy
m
pt
om
 im
pr
ov
ed
4
29
F
FO
LF
OX
1
Vi
su
al
 lo
ss
 a
ffe
ct
in
g 
th
e 
lo
w
er
 h
al
f o
f  
th
e 
vi
su
al
 fi
el
d
Ox
al
ip
la
tin
 w
as
 d
is
co
nt
in
ue
d,
 a
nd
 th
e 
re
gi
m
en
 ch
an
ge
d,
  
an
d 
th
e 
sy
m
pt
om
 im
pr
ov
ed
5
[8
]
20
07
58
F
FO
LF
OX
2
Bl
ep
ha
ro
pt
os
is
Th
e 
sy
m
pt
om
 im
pr
ov
ed
 sp
on
ta
ne
ou
sl
y
Ox
al
ip
la
tin
 w
as
 d
is
co
nt
in
ue
d,
 a
nd
 th
er
e 
w
as
 n
o 
re
cu
rr
en
ce
  
of
 th
e 
sy
m
pt
om
6
72
F
Ox
al
ip
la
tin
  
m
on
ot
he
ra
py
1
Bl
ep
ha
ro
pt
os
is
Th
e 
sy
m
pt
om
 im
pr
ov
ed
 sp
on
ta
ne
ou
sl
y
Ox
al
ip
la
tin
 w
as
 co
nt
in
ue
d 
w
ith
ou
t r
ec
ur
re
nc
e 
of
 th
e 
sy
m
pt
om
7
[9
]
20
09
76
F
EO
X
2
Bl
ep
ha
ro
pt
os
is
Th
e 
tim
e 
sp
en
t a
dm
in
is
te
ri
ng
 o
xa
lip
la
tin
 w
as
 e
xt
en
de
d 
fr
om
  
cy
cl
e 
6,
 a
nd
 th
e 
sy
m
pt
om
 im
pr
ov
ed
8
[1
0]
20
10
52
F
FO
LF
OX
3
Bl
ur
re
d 
vi
si
on
 a
nd
 a
lte
re
d 
co
lo
r v
is
io
n
Th
e 
sy
m
pt
om
 im
pr
ov
ed
 p
ro
gr
es
si
ve
ly
 3
 w
ee
ks
 a
fte
r  
ch
em
ot
he
ra
py
 w
as
 d
is
co
nt
in
ue
d
9
[1
1]
20
19
71
M
FO
LF
IL
IN
OX
1
Tu
nn
el
 v
is
io
n 
of
 th
e 
ri
gh
t e
ye
W
ith
 ch
an
ge
 o
f t
he
 ch
em
ot
he
ra
pe
ut
ic
 re
gi
m
en
, t
he
re
 w
as
  
no
 re
cu
rr
en
ce
 o
f t
he
 sy
m
pt
om
10
Ou
r c
as
e
20
21
70
M
SO
X
1
Vi
su
al
 lo
ss
 a
ffe
ct
in
g 
th
e 
ri
gh
t h
al
f o
f  
th
e 
vi
su
al
 fi
el
d 
in
 th
e 
ri
gh
t e
ye
Ox
al
ip
la
tin
 w
as
 d
is
co
nt
in
ue
d 
fr
om
 cy
cl
e 
6 
an
d 
th
er
e 
w
as
  
no
 re
cu
rr
en
ce
 o
f t
he
 sy
m
pt
om
FO
LF
OX
, o
xa
lip
at
in
 +
 fl
uo
ro
ur
ac
il 
+ 
le
uc
ov
or
in
; E
OX
, e
pi
ru
bi
ci
n 
+ 
ca
pe
ci
ta
bi
ne
 +
 o
xa
lip
la
tin
; F
OL
FI
RI
N
OX
, o
xa
lip
la
tin
 +
 ir
in
ot
ec
an
 +
 fl
uo
ro
ur
ac
il 
+ 
le
uc
ov
or
in
; S
OX
, 
S-
1 
+ 
ox
al
ip
la
tin
.
*C
he
m
ot
he
ra
py
 cy
cl
e 
nu
m
be
r a
t a
pp
ea
ra
nc
e 
of
 sy
m
pt
om
s.
836Case Rep Oncol 2021;14:832–837
Kubo et al.: Amaurosis Fugax
www.karger.com/cro
© 2021 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000516271
the patient was diagnosed with oxaliplatin-associated amaurosis fugax, based on the ophthal-
mologist’s diagnosis.
The other implication was that carotid artery lesions were excluded in diagnosing amau-
rosis fugax. It has been reported that causes of amaurosis fugax include carotid artery lesions, 
heart disease, coagulation abnormalities, and vasculitis, 88% of which are closely related to 
carotid artery lesions [12], where microembolism in carotid artery stenosis or occlusion 
often leads to occlusion of the ophthalmic artery [13]. In the present case, carotid plaque and 
stenosis were excluded by MRI and carotid artery ultrasound. While oxaliplatin has been 
reported to lead to damage to the retinal pigment epithelium and the optic nerve [10], with 
no abnormalities found in the retinal and optic nerves in our case, the mechanism of oxali-
platin-associated amaurosis fugax remain unclear. To the best of our knowledge, this is the 
first report describing the clinical course and treatment of oxaliplatin-associated amaurosis 
fugax.
Statement of Ethics
Written informed consent was obtained from the patient for publication of this case 
report and any accompanying images.
Conflict of Interest Statement
The authors have no conflicts of interest to disclose in association with this study.
Funding Sources
The authors received no funding for this research.
Author Contributions
K.K., N.K., R.W., M.H., M.T., and M.K. contributed equally to the study as well as to the 
preparation of the manuscript for publication.
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Oxaliplatin-Associated Amaurosis Fugax

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Oxaliplatin-Associated Amaurosis Fugax

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