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SHORT–TERM EFFECTS OF
INTRAVITREAL BEVACIZUMAB FOR
NEOVASCULARIZATION IN PATHOLOGIC
MYRIAM L. HERNA
NDEZ-ROJAS, MD,* HUGO QUIROZ-MERCADO, MD,*
DALMA-WEISZHAUSZ, MD,* JANS FROMOW-GUERRA, MD, MS
S AMAYA-ESPINOSA, MD,*† ADRIANA SOLI
N, MD,* MAURA ABRAHAM-MARI
MARIA ANA MARTI
LLOYD P. AIELLO, MD, P
Purpose: To determine short–term effects of intravitreal bevacizumab for subfoveal
choroidal neovascularization (CNV) in pathologic myopia.
Methods: In this prospective interventional case series, patients were treated with 2.5
mg of intravitreal bevacizumab and followed for 3 months. Best-corrected visual acuity
(BCVA), optical coherence tomography (OCT), and ﬂuorescein angiography (FA) were
recorded. Indications for retreatment were active leaking CNV shown by FA and presence
of subretinal ﬂuid by OCT in combination with visual disturbances.
Results: Fourteen patients were included, with a mean age of 53.86 ⫾ 16.26 years
(range 29– 85). Mean spherical equivalent was ⫺13.87 ⫾ 3.68 diopters (⫺7.25 to ⫺20.50).
Minimum follow-up was 3 months. There were no adverse events. The mean initial visual
acuity was 20/200 improving to 20/100 at 2 weeks, 20/80 at 4 weeks, and 20/60 at 8 and
12 weeks (P ⫽ 0.007; P ⫽ 0.001; P ⫽ 0.005; P ⫽ 0.001, respectively). Initial foveal
thickness improved from 385.43
m ⫾ 125.83
m to 257.64 ⫾ 76.6
m and 194.54 ⫾
m after the ﬁrst and third month, respectively (P ⫽ 0.001).
Conclusions: Initial treatment results of patients with CNV due to pathologic myopia did
not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a signiﬁcant
decrease in foveal thickness and improvement in visual acuity. These favorable initial
results support further larger and long-term studies.
RETINA 27:707–712, 2007
igh myopia is a major cause of legal blindness in
many developed countries.
It affects approxi-
mately 2% of the general population
myopic eyes. The pathogenesis of high myopia is
associated with progressive and excessive elongation
of the anteroposterior axis of the eye.
myopic eyes, the collagen ﬁbers are pathologically
abnormal and the smaller ﬁbers have less cross linking
than those of emmetropic eyes.
These factors pre-
dispose to the development of various degenerative
changes involving the sclera, choroid, and retina. In
highly myopic eyes, elongation of the axial length
stretches the retinal pigment epithelium, causing atro-
From *Hospital Luis Sa´nchez Bulnes, Asociacio´n Para Evitar la
Ceguera en Me´xico I.A.P., Me´xico City, Me´xico; and †Beetham
Eye Institute, Joslin Diabetes Center, Department of Ophthalmol-
ogy, Harvard Medical School, Boston, Massachusetts.
No authors have a proprietary interest.
Reprint requests: Myriam L. Hernandez-Rojas, MD, Vicente
Garcia Torres #46 Col. San Lucas Coyoacan C.P. 04030 Mexico
D.F., Mexico; e-mail: firstname.lastname@example.org
phy and breaks in Bruch membrane observed clini-
cally as lacquer cracks, which are thought to facilitate
the development of choroidal neovascularization
A number of studies have demonstrated that vascu-
lar endothelial growth factor (VEGF), a potent mito-
gen for endothelial cells, plays a central role in the
development of neovascularization in various chori-
Stretching of the retinal pigment
epithelium was reported to upregulate the expression
and secretion of VEGF in retinal epithelium cells in
Myopic maculopathy, consisting of chorioretinal
atrophy and macular CNV, is the most common cause
of vision loss in highly myopic patients.
myopic CNV is a small, ﬂat, grayish, subretinal mem-
brane which is less than 1 disk diameter
located between the neurosensory retina and retinal
pigment epithelium (Type 2).
approaches have been employed to treat myopic
maculopathy, including the use of thermal laser pho-
photodynamic therapy (PDT),
more recently, antiangiogenic therapy.
Several antiangiogenic drugs are being tested for the
management of CNV. Bevacizumab (Avastin, Genen-
tech Inc., San Francisco, CA) is a monoclonal antibody
that blocks all isoforms of VEGF that has been used
clinically to treat colorectal cancer.
Recent reports have
suggested that bevacizumab delivered by intravitreal ad-
ministration may inhibit by neovascularization and prove
useful for treating CNV.
In this study we evaluate the effects of intravitreal
bevacizumab on CNV due to pathologic myopia.
Patients and Methods
This was a prospective, interventional, longitudinal
case series of patients with CNV due to pathologic
myopia recruited at the Retina Service of “Dr. Luis
Sa´nchez Bulnes” Hospital from the “Asociacio´n Para
Evitar la Ceguera en Me´xico” from September 2005 to
Inclusion criteria were refractive error of ⫺6.00 D
spherical equivalent or more, clear media, dilated pupil
size ⱖ4 mm, and presence of choroidal neovasculariza-
tion conﬁrmed by ﬂuorescein angiography (FA). Exclu-
sion criteria were heart disease, uncontrolled systemic
hypertension, diabetes, ﬂuorescein allergy, pregnancy,
use of intraocular toxic drugs, and any other retinal
Initial evaluation included manifest refraction, best-
corrected visual acuity (BCVA) evaluated by ETDRS
testing (Lighthouse International, NY) under standard
conditions, slit lamp examination, tonometry, fundus
examination using indirect ophthalmoscopy and slit
lamp, FA, and optical coherence tomography (OCT).
After informed consent and discussion of therapeu-
tic options, patients were treated with intravitreal in-
jection of 0.1 mL (2.5 mg) of bevacizumab, 4 mm
posterior to the limbus, in the superotemporal quad-
rant under aseptic conditions.
Patient follow-up was at 1, 2, 4, 8, and 12 weeks after
intravitreal injection. On each evaluation BCVA, com-
plete ocular examination, and blood pressure measure-
ment was performed. Fluorescein angiography and OCT
were done at 4 and 12 weeks after treatment.
Retreatment was considered if there was persistence
of subretinal ﬂuid on clinical evaluation or by OCT,
active leakage on FA, or decrease in visual acuity
associated with leakage at the late phases of the FA.
Fourteen eyes of 14 patients were treated. Ten
(71.4%) were female. The mean age was 53.86 ⫾
16.26 (29 – 85 years). Mean spherical equivalent was
⫺13.87 ⫾ 3.68 D (⫺7.25 to ⫺20.50 D). Choroidal
neovascular membranes were classiﬁed as subfoveal
classic in 12 patients (85.7%), juxtafoveal classic in 1
(7.1%), and subfoveal occult in 1 (7.1%).
There were no adverse effects noted after the intra-
vitreal injection of bevacizumab, for the duration of
the study. The mean initial visual acuity was 20/200
(logMAR ⫺0.95) which improved to 20/100 (logMAR
⫺0.70) 2 weeks after treatment, 20/80 (logMAR ⫺0.62) at
4 weeks, 20/60 (logMAR ⫺0.56) at 8 weeks, and at 12
weeks the BCVA averaged 20/60 (logMAR ⫺0.56)
(GLM repeated measures pairwise comparisons: P ⫽
0.007; P ⫽ 0.001; P ⫽ 0.005; P ⫽ 0.001, respec-
tively) (Figure 1).
Thirteen patients (92.8%) had 12 weeks follow-up.
One patient was lost to follow-up at week 6. Beneﬁts
from bevacizumab were seen as early as 2 weeks after
injection. At this time, visual acuity in 2 patients
(14.2%) was unchanged, improved 5 to 15 letters in 10
patients (71.4%), and improved more than 15 letters in
2 patients (14.2%). After 4 weeks of follow-up one
patient (7.1%) lost less than 5 letters, 9 patients
(64.2%) gained 5 to 15 letters, and 4 patients (28.5%)
gained more than 15 letters acuity. At the 12-week
follow-up visit all patients had gained more than 5
letters: 7 (50%) gained 5 to 15 letters and 6 (42.8%)
gained more than 15 letters (Table 1).
Mean foveal thickness by OCT was 385.43
m which decreased to 257.64 ⫾ 76.6
194.54 ⫾ 54.35
m at the ﬁrst and third month respec-
tively (Wilcoxon signed rank test P ⫽ 0.001) (Figure 2).
708 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
The amount of reduced thickness was 33.1 and 50
respectively (Figures 3 and 4).
Four eyes (28.6%) had persistent leakage on FA
and OCT associated with decreased visual acuity and
required retreatment after 5 ⫾ 1.09 weeks.
In pathologic myopia, CNV causes visual loss in
5–10% of patients.
Choroidal neovascularization in
high myopia is often considered self-limited; how-
ever, long-term follow-up has demonstrated poor
prognosis due to RPE atrophy.
Direct laser photocoagulation is no longer an indica-
tion for subfoveal CNV since it causes a full thickness
burn lesion in the retina which results in an irreversible
and a high incidence of recurrences.
Surgical removal of the CNV, though achieving good
anatomical results, often causes loss in retinal pigment
epithelium cells and poor ﬁnal visual acuity.
macular surgery has been evaluated for myopic CNV in
several studies with conﬂicting outcomes.
The VIP study is the largest study addressing the
efﬁcacy and safety of PDT with verteporﬁn in the treat-
ment of subfoveal CNV associated with myopia.
months, 72% of verteporﬁn-treated eyes compared with
44% of placebo-treated eyes had a visual loss of less than
eight letters, which was the primary outcome measure.
Moreover, 14% of the verteporﬁn treated group com-
pared with 33% of the placebo group developed moder-
ate visual loss of 15 letters or more. In this study, after 24
months follow-up, visual improvement of 5 letters (1
line) was noted in treated patients with PDT of 40%
versus 13% of placebo group.
Prospective, randomized, multicenter, double-masked
Fig. 1. Mean values ⫾ SDs
of visual acuity over time (in
weeks) in choroidal neovas-
cularization in pathologic my-
opia that was treated with in-
travitreal bevacizumab. An
improvement of visual acuity
Table 1. Frequency Distribution of Changes in Visual Acuity From Baseline in Choroidal Neovascularization in
Pathologic Myopia Treated With Intravitreal Bevacizumab
Change From Baseline in Visual Acuity
Patients, n (%)
2wk 4wk 8wk 12wk
ⱕ⫺1 Line (loss ⬍5 letters) 0 (0) 1 (7.1) 1 (7.1) 0 (0)
0 Lines (maintenance or gain ⬎0 letters) 2 (14.3) 0 (0) 0 (0) 0 (0)
1 to 3 lines (gain 5 to 15 letters) 10 (71.4) 9 (64.3) 4 (26.6) 7 (50)
ⱖ3 Lines (gain ⬎15 letters) 2 (14.3) 4 (26.6) 7 (50) 6 (42.9)
709INTRAVITREAL BEVACIZUMAB FOR CNV
NDEZ-ROJAS ET AL
studies reported the 2-year safety proﬁle of pegaptanib
sodium (Macugen, Eyetech Pharmaceuticals, New York,
NY) in patients with exudative AMD
using ranibizumab for treatment of neovas-
cular age-related macular degeneration (AMD) had a
good safety proﬁle and were well tolerated and biologi-
cally active in eyes with neovascular AMD.
Michels et al
evaluated the short-term safety of
Fig. 2. Mean values ⫾ SDs
of retinal thickness (measured
by optical coherence tomog-
raphy) over time (in months)
in choroidal neovasculariza-
tion in pathologic myopia that
was treated with intravitreal
bevacizumab. A signiﬁcant
decrease in thickness over
time (P ⫽ 0.001) is observed.
Fig. 3. Fundus photograph
of a patient with myopic
(CNV). A CNV with subreti-
nal hemorrhage is noted at
baseline. At 4 weeks resolu-
tion of the subretinal hemor-
rhage is noted with a decrease
in foveal thickness by optical
coherence tomography. A
small residual subretinal ﬁ-
brotic lesion is seen at 12
weeks with no subretinal
710 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
systemic bevacizumab for CNV AMD and it was well
tolerated, with an improvement in VA, OCT, and
Nguyen et al
treated two patients with intravenous
infusions of bevacizumab (5 mg/kg) to CNV caused
by pathologic myopia and reported anatomical and
Our initial results show that intravitreal bevaci-
zumab produces a statically signiﬁcant and clinical
meaningful beneﬁt in visual acuity and retinal thick-
ness in patients with CNV associated with pathologic
myopia. This effect is observed as early as 2 weeks
after treatment and becomes increasingly evident over
the course of the 3-month follow-up.
Although eyes with hyperﬂuorescence with well-
deﬁned borders but increasing hyperﬂuorescence at
late phases of the FA might be considered to be
leaking actively and in need of retreatment, these eyes
were only treated in presence of activity measured by
OCT. Although 4 patients (28%) required retreatment
after 5 ⫾ 1.09 weeks, all of them were considered
inactive after 12 weeks of follow-up.
Reports of intravenous use of bevacizumab have
mentioned complications including gastrointestinal
bleeding and systemic hypertension.
We found no
short-term side effects, either local or systemic,
associated with intravitreal bevacizumab. Limiting
factors of our study include the few participants,
short–term follow-up, and the absence of a control
The potential clinical beneﬁt of intravitreal bevaci-
zumab will only be known after careful long-term
studies speciﬁcally evaluating the safety proﬁle and
efﬁcacy of this therapeutic approach. However, the
current study demonstrated short-term beneﬁt without
observed side effects and thus supports future evalu-
ation of this promising pharmacologic approach for
treating CNV from pathologic myopia.
Key words: antiangiogenic therapy, subfoveal
choroidal neovascularization, pathologic myopia,
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