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Brito RC et al. Intravitreal Ranibizumab in macular edema secondary to malignant hypertension.
Intravitreal Ranibizumab for the
treatment of macular edema secondary
to malignant hypertension
Raquel C. Brito, MD, Pedro Neves, MD, Inês Matias, MD, Mário Ornelas, MD,
David Martins, MD
From Department of Ophthalmology, São Bernardo Hospital,
Setúbal, Portugal
Corresponding author: Raquel Claro Brito, MD
Rua Direita de Massamá, nº125 – 7ºA. 2745-756 Massamá, Portugal
Telephone: (+351) 215903433/ (+351) 969905827
Email: [email protected]
¹ Professor of Ophthalmology.
² Resident in Ophthalmology.
³ Medical Undergraduate.
Funding: None
Proprietary/financial interes: None
ABSTRACT
Our purpose is to report a
clinical case of bilateral macular
edema caused by malignant
hypertension in a 35-year old male.
Patient presented with bilateral
low visual acuity, massive macular
edema, retinal hemorrhages and
papilledema. Soon after he was
diagnosed with other target-organ
lesions, on heart and kidneys. After
6 months of controlled blood
pressure, an increase in visual acuity
and a small decrease of macular
edema, we effectively treated
the lower vision eye with two
intravitreal ranibizumab injections,
improving anatomy and function
on both eyes. Even though we only
treated one eye with ranibizumab,
the contralateral eye also improved
visual acuity and central macular
thickness. This probably happened
due to systemic absorption of
ranibizumab. To the best of our
knowledge, this is the first report of
ranibizumab use in macular edema
due to malignant hypertension.
Keywords: Malignant
hypertension; macular edema;
ranibizumab.
INTRODUCTION
Malignant hypertension is a
rare hypertensive emergency in
which systolic blood pressure is
higher than 200 mmHg and/or
diastolic blood pressure is higher
V I S I O N
Date of submission: 14/10/2015
Date of approval: 29/11/2015
than 140 mmHg and targetorgan lesions are present.1,2 Its
ocular manifestations are due to
vascular constriction, arteriolar
obstruction and blood-ocular
barrier disruption, and retinopathy,
choroidopathy
and
optic
neuropathy.3,4 Without treatment,
the mortality rate is higher than
90% in one year.1
CASE REPORT
A 35-year-old caucasian
male patient, with no relevant
medical history, came for urgent
ophthalmologic
evaluation
because of bilateral progressive
blurred vision and holocranial
headache for the past two
weeks. Best-corrected visual
acuity (BCVA) on the right eye
(OD) was counting fingers and on
the left eye (OS) was 0,1. Pupillary
reflexes were symmetric and
slow, medium were clear and
the average intraocular pressure
was 14 mmHg on OD and 13
mmHg on OS. Fundoscopy of
both eyes showed flame and dot
hemorrhages in all quadrants,
retinal edema with massive
macular edema, hard exudates
in the macula forming a macular
star and disc edema (Figure
1). Macular optical coherence
tomography (OCT) revealed a
central macular thickness (CMT)
of 984 µm and 968 µm on OD and
OS, respectively (Figure 2). Blood
P A N - A M E R I C A N
–
T H E
Figure 1. Fundoscopy of both eyes showed flame and dot hemorrhages in all quadrants, retinal edema
with massive macular edema, hard exudates in the macula forming a macular star and disc edema.
P A N - A M E R I C A N
Figure 2. Macular OCT revealed massive macular edema on
both eyes.
J O U R N A L
O F
O P H T H A L M O L O G Y
Vis. Pan-Am. 2016; 15(1): 21-22.
Figure 3. Fluorescein angiography.
of
choroidal
fluorescence
by
retinal
hemorrhages,
multiple microaneurysms in
the peripapillary region, and
fluorescein leakage in late phases
related to the retinal edematous
areas (Figure 3).
Figure 4. Macular OCT, 4 months after diagnosis and blood
pressure control.
Figure 5. Retinography, 4 months after diagnosis, retinal hemorrhages were reabsorbed, disc
edema resolved and a preretinal hemorrhage was seen on OS.
After
4
months
of
ophthalmologic observation only,
and normal blood pressure levels,
BCVA increased to 0,1 on OD and
0,6 on OS, and CMT decreased
to 644 µm on OD and 600 µm
on OS (Figure 4). Most of retinal
hemorrhages were reabsorbed,
disc edema resolved and a
preretinal hemorrhage was seen
on OS (Figure 5). After 6 months,
BCVA remained stable but CMT
lightly increased, so we decided
to treat only the eye with lower
visual acuity, the right eye, with
intravitreal ranibizumab 0,5 mg.
CMT returned to normal on both
eyes after two injections with
one month interval (Figure 6), and
BCVA improved to 0,3 and 0,8 on
OD and OS, respectively. After two
years of follow-up, CMT and visual
acuity are stable, as well as blood
pressure levels. and anatomic retinal profile on
macular OCT. Initially, in malignant
hypertension, there is vascular
constriction in choroidal and
retinal vasculatures that cause
ischemia, and these are followed
by vasodilation and increased
vascular permeability. Induced
retinal edema, in turn, produces
more ischemia and vascular
endothelial
growth
factor
release, which can be blocked by
intravitreal ranibizumab.
Even though we only treated
the right eye with ranibizumab,
the left eye also improved BCVA
and CMT. We think this happened
because of systemic absorption
of ranibizumab, despite the fact
that ranibizumab is a monoclonal
antibody fragment, having a
shorter systemic half-life without
the Fc domain, of about 2 hours
after entering systemic circulation
from the eye.5 And besides the
fact that systemic absorption of
ranibizumab given intravitreally
seems to be minimal.
Final OCT shows IS/OS line
distortion and retinal pigment
epithelium atrophy on OD, signs
of irreversible damage of the
retina, that can explain the low
visual acuity of the treated eye,
even after the achievement of a
normal macular thickness.
References
1.
Shantsila A, Shantsila E, Lip
GY. Malignant hypertension: a
rare problem or is it underdiagnosed? Curr Vasc Pharmacol.
2010;8(6):775-9.
2.
Tajunisah I, Patel DK. Malignant
hypertension with papilledema. J
Emerg Med. 2013; 44(1):164-5.
3.
Hayreh SS, Servais GE. Retinal
hemorrhages in malignant arterial
hypertension. Int Ophthalmol.
1988;12(2):137-45.
4.
Tajunisah I, Patel DK. Images in
clinical medicine. Retinal detachment in malignant hypertension. N
Engl J Med. 2009;27-361(9):899.
5.
Avery RL, Castellarin AA, Steinle
NC et all. Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab
or aflibercept in patients with
neovascular AMD. Br J Ophthalmol. 2014;98(12):1636-41.
DISCUSSION
Figure 6. Macular OCT showing normal CMT on both eyes after two injections of ranibizumab
on OD.
pressure was 241/146 mmHg,
and the patient was referred
for emergent blood pressure
control. He was diagnosed
with acute renal insufficiency
requiring emergent hemodialysis
and cardiac markers for ischemia
were elevated. Two weeks
later, fluorescein angiography
showed delayed choroidal filling
in the early phases, blocking
22
In this clinical case, malignant
hypertension was the first
manifestation
of
systemic
hypertension, which is rare,
but must be kept on mind.
The recognition of malignant
hypertension has implications
for the eye and general health of
patients.
Intravitreal
ranibizumab
0,5 mg was effective in the
treatment of macular edema
due to malignant hypertension,
improving both visual function