a r c h s o c e s p o f t a l m o l .

2 0 1 2;8 7(1 2):396400

ARCHIVOS DE LA SOCIEDAD
ESPAOLA DE OFTALMOLOGA
www.elsevier.es/oftalmologia

Original article

Intracameral bevacizumab (Avastin ) in the management

of neovascular glaucoma surgery,
H. Fernndez Jimnez-Ortiz , S. Perucho Martinez,
N. Toledano Fernndez, E. Martin Giral
Servicio de Oftalmologa, Hospital Universitario de Fuenlabrada, Madrid, Spain

a r t i c l e

i n f o

a b s t r a c t

Article history:

Purpose: To describe a case series of neovascular glaucoma treated with intracameral beva-

Received 21 January 2011

cizumab prior to ltering surgery.

Accepted 11 September 2011

Design: Descriptive, retrospective case series.

Available online 22 January 2013

Methods: Five eyes of 5 patients with neovascular glaucoma due to any cause candidates

Keywords:

(1.25 mg/0.05 ml) as treatment for neovascularization of anterior chamber. Results observed

Bevacizumab

one week and 4 weeks post-surgery are reported.

to ltering surgery who had previously received an injection of intracameral bevacizumab

Glaucoma neovascular

Results: Bevacizumab produced regression of the angle neovascularization and the intraoc-

Filtering surgery

ular pressure. Only one case of postoperative bleeding was detected.

Angiogenesis inhibitors

Conclusions: Intracameral bevacizumab prior to ltering surgery of neovascular glaucoma

Injections intraocular

diminished the neovascularization and intraocular pressure after 4 weeks of its administration and was effective in preventing intraoperative and postoperative bleeding. It also
constitutes a promising way of investigation to prevent surgical complications.
2011 Sociedad Espaola de Oftalmologa. Published by Elsevier Espaa, S.L. All rights
reserved.

Bevacizumab (Avastin ) intracamerular en el manejo quirrgico

del glaucoma neovascular
r e s u m e n
Palabras clave:

Propsito: Describir una serie de casos con glaucoma neovascular que fueron tratados con

Bevacizumab

bevacizumab intracamerular previo a la ciruga ltrante.

Glaucoma neovascular

Descriptivo, retrospectivo, tipo serie de casos.

Diseno:

Ciruga ltrante

Mtodos: Cinco ojos de cinco pacientes con glaucoma neovascular de cualquier causa

Antiangiognicos

candidatos a ciruga ltrante recibieron previamente una inyeccin de bevacizumab

Inyeccin intraocular

(1,25 mg/0,05 ml) intracamerular como tratamiento de la neovascularizacin angular. Se

describen los resultados observados a la semana y a las 4 semanas posciruga.
Resultados: Bevacizumab produjo una regresin importante de los neovasos y de la presin
intraocular. Se detect un nico caso de sangrado postoperatorio.

Please cite this article as: Fernndez Jimnez-Ortiz H, et al. Bevacizumab (Avastin ) intracamerular en el manejo quirrgico del
glaucoma neovascular. Arch Soc Esp Oftalmol. 2012;87:396400.

This paper was presented at the VI International Iberian-American Congress in Havana, May 2009.

Corresponding author.
E-mail address: hector fernan@hotmail.com (H. Fernndez Jimnez-Ortiz).

2173-5794/$ see front matter 2011 Sociedad Espaola de Oftalmologa. Published by Elsevier Espaa, S.L. All rights reserved.

a r c h s o c e s p o f t a l m o l . 2 0 1 2;8 7(1 2):396400

397

Conclusiones: Bevacizumab intracamerular previo a ciruga ltrante de glaucoma disminuy

la neovascularizacin del segmento anterior y la presin intraocular a las 4 semanas de
su administracin y result ecaz en impedir el sangrado intra- y postoperatorio. Tambin constituye una prometedora va de investigacin para prevenir las complicaciones
quirrgicas.
2011 Sociedad Espaola de Oftalmologa. Publicado por Elsevier Espaa, S.L. Todos los
derechos reservados.

Introduction
Bevacizumab ([BVI]: Avastin , Genentech, Inc., South San
Francisco, CA) is a recombinant monoclonal antibody with
specicity for all the active isoforms of the endothelial vascular growth factor A (VEGF-A).1 It was designed for intravenous
use and approved in 2004 for metastatic colorectal cancer in combination with chemotherapy. To date, intraocular
administration of bevacizumab is not approved.2 However,
numerous papers suggest it has a benecial role in ophthalmic
use.
In 1998, Tripathi et al.3 documented the increase of VEGF-A
in the aqueous humor of patients with neovascular glaucoma (NVG). Mason et al.4 proposed intravitreous BVI for
patients with NVG, recurring hemorrhage of iridian neovessels and those with neovessels despite panphotocoagulation
(PFC). Jonas et al.5 documented in 2 cases the normalization
of intraocular pressure (IOP) with the use of intravitreous BVI
together with ltration surgery in NVG. Andreoli and Miller6
proposed the use of intravitreal BVI in patients who underwent panphotocoagulation to avoid the complete closure of
the angle while it takes effect.
The administration of BVI in posterior segment neovascularization processes is broadly documented.5,7,8 However,
intra-chamber administration can also be benecial in
anterior segment neovascularization processes (Fig. 1).6,812
Wakabayashi et al.13 observed adequate control of IOP in
patients with NVG without the closure of the angle if administered in early stages. Recently, a series of 6 cases14 with
neovascular glaucoma and BVI injection prior to panphotocoagulation or ltrating surgery was published. The publication
suggested the adjuvant effect of this technique when applied

Fig. 1 Rubeosis iridis and iridian synechiae

in pharmacological midriasis.

prior to surgery. It seems that IOP can be poorly controlled in

advanced stages even though surgical results improved when
applying BVI as an adjuvant.
The only comparative study that the authors have found is
a retrospective series of cases in which Chen et al.15 found
improved visual acuity in a six-month follow-up. In patients
with NVG treated with intravitreous BVI or plus trabeculectomy compared with trabeculectomy on its own.
The objective of this study is to describe a series of cases
with neovascular glaucoma treated with BVI intrachamber
prior to glaucoma ltrating surgery.

Subjects, materials and methods

The database of the Fuenlabrada University Hospital was
searched to select the clinical records with the following inclusion criteria:
- NVG due to any cause. NVG was taken to be a sustained IOP
of 21 mmHg as a consequence of an ocular ischemia process and the presence of neovascularization in the anterior
segment or irido-corneal angle.
- Candidate for NVG surgical treatment with ltrating surgery
and administration of BVI (single dose of 1.25 mg/0.05 ml)
intrachamber 24 h prior to surgery.
The Ahmed valve was implanted in all surgeries because
our hospital has more experience with it. The indication for
surgery was established in the case of failed IOP and symptomatic control despite having received PFC and at least 2
ocular hypotensor drugs.
The cases that previously received any dose of intraocular
or systemic antiangiogenic drug (BVI, ranibizumab or pegaptanib) were excluded.
It was considered that intrachamber administration
excluded some of the risks involved in intravitreal injection
such as iatrogenic cataracts, retinal regmatogenous lesions
or subconjunctival drug diffusion. As the purpose was to act
upon iris and angle neovascularization, that intrachamber
pathway allowed the action of BVI on the NVG vessels, involving lower risk for the eye.
The BVI injection in the anterior chamber was done with a
30 g and assisted by surgical microscope.
The patients were informed verbally and in writing that
the indication of intrachamber BVI is based on compassionate use due to the current lack of evidence recommending its
administration. All patients signed the appropriate informed
consent.
All the variables considered to be relevant to describe the
effect of intrachamber BVI in ltrating surgery were analyzed

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Table 1 Characteristics of study cases.

Case 1
Case 2
Case 3
Case 4
Case 5

Age

Sex

62
83
33
58
33

V
M
V
V
V

Previous
glaucoma

Cause of
neovascularization

No
No
No
No
OHT postuveitis

PDR
PDR
CRVT
PDR
Unknown

Follow-up
(weeks)

7
24
18
13
10

Previous
treatments

PFC, FC
PFC, FC, BCZv
PFC, B/T, ATR, ACZ, DXT
PFC, B/T, ACZ
PFC, D/T, DXTc

Intra-op
bleeding

Immediate
postop bleeding
(<48 h)

No
No
No
No
No

Yes
No
No
No
No

ACZ: oral acetazolamide; ATR: atropin in eyedrops; B/T: brimonidin tartrate/timolole maleate in eyedrops; BCZv: intravitreous bevacizumab;
D/T: dorzolamide/timolole in eyedrops; DXT: oral dexametasone; DXTc: dexametasone eyedrops; FC: phakotrabeculectomy; OHT: ocular hypertension; F: female; PFC: panphotocoagulation; PDR: proliferative diabetic retinopathy; CRVT: central retina vein thrombosis; M: male.

Table 2 Intraocular pressure prior to bevacizumab and at weeks 1 and 4.

Intraocular pressure (mmHg)
One week assessment

4 week assessment

35
30
38
40
43
37.2 4.9 (CI 95%)

7
14
40
12
13
17.2 13.02 (CI 95%)

13
16
28
22
16
19.0 6.0 (CI 95%)

(Tables 1 and 2). The main variable was anterior chamber

bleeding either during or after surgery. The analyzed data
were collected 2448 h prior to the injection and one week and
4 weeks after it.
SPSS version 11.5 (SPSS Inc., Chicago, IL) statistical software was utilized to analyze the data. After verifying that the
distribution of variables did not t normality by means of the
KolmogorovSmirnov tests, nonparametric tests were applied.
The T for student for paired data was used to compare the
IOP results before and after the intervention. The main variable was studied on the basis of percentage and a condence
interval (IC) of 95%.

Results
The samples comprised 5 eyes of 5 patients, 4 of them
females (80%) and one male (20%). The mean age was of
53.8 21.23 years (CI 95%). The mean follow-up time was
of 14.4 6.7 weeks (CI 95%). Vascularization causes were multiple: diabetic retinopathy in the cases, retina central vein
thrombosis in one and unknown etiology in the last case, possibly ocular ischemia syndrome. In all cases previous retinal
PFC had been performed (Table 1).
The initial IOP was the last one recorded before the BVI
injection, taken between 24 and 48 h earlier. The mean IOP
value was of 37.2 4.9 (CI 95%). The IOP values were recorded
one and 4 weeks after the injection (Table 2). Gonioscopy
revealed variable degrees of angular closure due to neovascularization in all cases (Fig. 1 and Table 3).
The comparison of mean values before and 4 weeks
after the injection was made applying the T for student
test for paired data. The results exhibit statistically signicant differences (Fig. 2); the initial IOP ranged between
42.1 and 32.3 mmHg and the IOP values 4 weeks after the

injection ranged between 26.00 and 13.00 mmHg with a

p = 0.043 (Table 2).
In what concerns the main variable, i.e., the intra-and
immediate postop (<24 h) bleeding which was taken to be
positive if exhibiting hyphema, hemovitreous or choroidal
hemorrhage, did not arise in any case during surgery and in
one case in the immediate postop (Table 1, Figs. 3 and 4).
Other recorded variables comprised angular neovascularization and maximum corrected visual acuity (MCVA) (Table 3).
In what concerns the latter, it was observed that in the rst
week assessment case 5 was the same and the remaining
cases had worsened. At week 4, 2 had worsened vis--vis the
baseline (cases 1 and 2) and the remainder were the same.
Rubeosis iridis improved in 3 patients at week 4 (cases 3, 4 and
5), remaining the same in one case (case 1) and worsening in a
further case (case 2) (Table 3). Said data match those observed
in the Wakabayashi et al. series for patients with NVG and

IOP difference Goldmann-Pascal(mm Hg)

Case 1
Case 2
Case 3
Case 4
Case 5
Medias

Initial

60

50

37.24.9 (CI 95%)

40

17.213.02 (CI 95%)

30

20

10
19.06.0 (CI 95%)
0
No. =

5
Initial

5
1 week

5
4 weeks

Fig. 2 Comparison of intraocular pressure mean values

at baseline, one week and 4 weeks after bevacizumab.

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a r c h s o c e s p o f t a l m o l . 2 0 1 2;8 7(1 2):396400

Table 3 Maximum corrected visual acuity and rubeosis iridis prior to bevacizumab and after one and 4 weeks.
Neovascularization in gonioscopy ( )

Maximum corrected visual acuity

Case 1
Case 2
Case 3
Case 4
Case 5

Initial

One week assessment

0.4
0.05
0.05
0.15
PL

PL
PL
FC2m
0.05
PL

4 week assessment
FC1m
PL
0.05
0.15
PL

Initial
0180
0180
180360
180360
360

4 week assessment
0180
360
0180
0180
0180

PL: perception of light; FC1m: nger counting at 1 m; FC2m: nger counting at 2 m.

Fig. 3 Hyphema in postop of ltrating surgery

with Ahmed valve.

closed angle.12 None of the cases required re-treatment with

BVI as pressure and symptomatic control was satisfactory.

Discussion
In what concerns the main variable of the study, it can be said
that no patient suffered intra-surgery bleeding and only one
had post-surgery bleeding (case 1: Table 1 and Fig. 3). In our
experience, intra- and post-surgery bleeding are considerably
more frequent without the use of BVI than in the samples,
which was of 0% and 20% respectively.
Published data on this topic refer hyphema frequencies in
the area of 11.4% in the rst month in a sample of 70 eyes

by Montanez
et al.16 and in the area of 5% in a sample of
10
9

Percentage

8
7

80%

6
5
4

20%

3
2
1
0
Yes

NO

Fig. 4 Frequency of post-surgery bleeding.

22 eyes by Luttrull and Avery.17 It is not possible to analyze

a comparison of hypotheses because all patients received the
same treatment. Likewise, we cannot compare our data with
said studies because they are non-analogous samples.
The effect over IOP is also due to ltrating surgery and
therefore we are unable to assess the magnitude of the effect
of intrachamber BVI.
With a sample as small as in this study it is not possible
to identify risk factors for the improvement or worsening of
the visual equity or rubeosis iridis. However, it must be emphasized that the only case that worsened had the differential
characteristic of previously receiving intravitreal BVI 5 weeks
earlier.
The risks of intrachamber BVI administration are endophthalmitis, retina detachment, cataracts and uveitis. None of
these effects were observed in our sample. In intravenous
administration hypertension, increased thromboembolic risk,
gastrointestinal perforation, mio collagen infarct and even
death have been observed.1
The serum levels of BVI after intravitreal administration are much lower than those reached after intravenous
administration.18 The VISION study19 which collected pharmacological safety data during a two-year period did not
reveal increases in cardiovascular diseases associated to systemic administration. The mean life of intravenous BVI is of
1721 days2 although the duration of the antiangiogenic effect
after administration and the existence of any type of permanent effect is yet to be determined.
In our sample, intrachamber BVI 24 h prior to the Ahmed
valve implant produced a low frequency of bleeding in the
anterior chamber and good IOP and symptom control at
week 4.
The above data allow us to suspect the benecial effect
of intrachamber BVI to prevent said complications. In addition, we consider that the intrachamber pathway involves
some advantages vis--vis the intravitreal pathway, including
diminished iatrogenic cataract risk because the tip of the needle can be seen at all times as well as the disappearance of
the risk of regmatogenous lesion or subconjunctival diffusion
of antiangiogenic. In addition, the concentration of BVI in the
anterior chamber would probably be higher than in intravitreal
administration, above all in phakic patients, which increases
the effect of the drug on anterior segment neovessels. Possible
toxic effects on the cornea did not seem clinically signicant
according to other studies carried out with intrachamber BVI
injections.14
At this time there are several studies which conrm the
rapid response of anterior segment neovascularization to BVI

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and its usefulness for controlling IOP, symptoms and prognosis of GNV.14.19 As in the posterior pole, the antiangiogenic
effect is limited in time and it is known that the BVI per se
does not enable controlling the antiangiogenic stimulus, making strict monitoring necessary together with treatment for
the underlying cause.20,21
Due to the lack of randomized clinical trials on the
intraocular use of BVI, many questions remain unanswered
including its absolute and compared efcacy vis--vis other
antiangiogenics, its posology (dosage, number and intervals
between the injections) and secondary intraocular and systemic effects.10,13
Intrachamber BVI for treating anterior segment neovascularization and preventing surgical complications constitutes a
promising path for research.

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