ORIGINAL STUDY
Management of Neovascular Glaucoma With Panretinal
Photocoagulation, Intravitreal Bevacizumab, and
Subsequent Trabeculectomy With Mitomycin C
Ayman A. Alkawas, MD, Ezzat A. Shahien, MD, and Atef M. Hussein, MD
Purpose: The aim of this study was to evaluate the safety and
efficacy of using intravitreal bevacizumab, panretinal photocoagu-
lation, and trabeculectomy with mitomycin C in the management
of neovascular glaucoma.
Patients and Methods: The study included 17 eyes of 15 patients
with neovascular glaucoma. Panretinal photocoagulation was
performed combined with intravitreal bevacizumab injection
(1.25 mg in 0.05 mL). A fornix-based conjunctival flap trabeculect-
omy with intraoperative mitomycin C (0.4mg/mL for 3min) was
then performed.
Results: The causes of neovascular glaucoma included: diabetic
retinopathy (10 eyes), central retinal vein occlusion (5 eyes), and
branch retinal vein occlusion (2 eyes). Complete regression of iris
neovascularization after intravitreal bevacizumab injection and
panretinal photocoagulation occurred in 14 eyes (82.4%). After
trabeculectomy with mitomycin C, mean intraocular pressure was
reduced from 42.9 ± 4.2 mm Hg preoperatively to 15.1 ± 2.2,
16.3 ± 2.0, and 19.7 ± 2.1 mm Hg at first week, first month, and
sixth months postoperatively, respectively. This reduction was
statistically significant (P<0.05). The mean number of antiglau-
coma medications used before surgery was 2.8 ± 0.4 (range: 2 to 3)
that decreased to 0.8 ± 0.6 (range: 0 to 3) after surgery. Post-
operative hypotony (intraocular pressure 7 mm Hg) was observed
in 17.6% (3 of 17 eyes), conjunctival dehiscence in 5.9%, shallow
anterior chamber in 11.8%, hyphema in 23.5%, choroidal
detachment in 11.8%, and epithelial corneal erosions related to
applications of mitomycin C in 1 eye (5.9%).
Conclusions: Trabeculectomy with intraoperative mitomycin C
after an adjunctive treatment with intravitreal bevacizumab and
panretinal photocoagulation is a good treatment modality in the
management of eyes with neovascular glaucoma.
Key Words: neovascular glaucoma, bevacizumab, panretinal
photocoagulation, trabeculectomy, mitomycin C
(J Glaucoma 2010;19:622–626)
A nterior segment neovascularization and neovascular
glaucoma (NVG) occur as a result of global ischemia.
NVG is a devastating disease. Its management is complex
and frequently requires the integrated use of medical, laser,
and surgical modalities. With the introduction of panretinal
photocoagulation (PRP) to eliminate the stimulus for
Received for publication March 12, 2009; accepted November 22, 2009.
From the Department of Ophthalmology, Faculty of Medicine,
Zagazig University, Egypt.
Reprints: Ayman A. Alkawas, MD, Algalaa Tower, Talaat Harb Square,
Zagazig, Sharkia, Egypt (e-mail: aymanalkawas@yahoo.com).
Copyright r 2010 by Lippincott Williams & Wilkins
DOI:10.1097/IJG.0b013e3181ccb794
622 | www.glaucomajournal.com
neovascularization, filtering surgery for NVG has been
more successful.1–3 Encouraging surgical results with the
use of ‘‘modified’’ filtration surgery have been reported in
several studies with short follow-up.4–6 In this modified
filtration surgery, after the ‘‘trabeculectomy’’ specimen has
been excised, light bipolar cautery is applied to the exposed
iris tissue in a semicircular manner. A careful broad-based
basal peripheral iridectomy is performed within the area of
previously cauterized iris. The 2 or 3 exposed ciliary
processes (a potential source of future neovascularization)
are then lightly cauterized with bipolar cautery. Care is
taken to avoid the lens equator.4
It has also been suggested that mitomycin C (MMC)-
augmented trabeculectomy may yield better results than
subconjunctival 5-fluorouracil (5-FU) application.7
The pathogenesis of NVG is linked to locally produced
angiogenic growth factor: vascular endothelial growth
factor (VEGF). In NVG and anterior segment neovascu-
larization, the level of VEGF in the aqueous humor is
significantly increased.8 Artificially elevating VEGF levels
in animal eyes was sufficient to result in neovascularization
of the iris (NVI) and NVG.9 Bevacizumab (Avastin,
Genentech) is a recombinant, full-length, anti-VEGF
monoclonal antibody that binds to all forms of VEGF-A.
It is Food and Drug Administration-approved for the
treatment of colorectal cancer.10 Bevacizumab causes
regression of NVI when injected into the vitreous or
anterior chamber.11 Regression occurs quickly, often within
1 week. However, bevacizumab’s duration of action is
short-lived, lasting about 4 weeks.12 Multiple case reports
have shown that after bevacizumab injection regression of
anterior segment neovascularization may persist for 4 to 10
weeks and no severe ocular or systemic side effects have
been reported.1,13–15 In most of these case reports, previous
or concomitant PRP was applied, limiting extrapolation of
the duration of isolated bevacizumab effect.16,17 Duch
et al16 studied the use of intracameral bevacizumab (ICB) in
6 patients with NVG as the first maneuver before PRP and/
or filtering surgery. ICB resulted in a marked regression of
anterior segment neovascularization with intraocular pres-
sure (IOP) control without filtering surgery in 2 cases.
The aim of this study was to evaluate the safety and
efficacy of intravitreal bevacizumab (IVB; Avastin) injec-
tion, PRP, and trabeculectomy with intraoperative MMC
in the management of eyes with NVG.
PATIENTS AND METHODS
Fifteen patients (17 eyes) with NVG presenting to the
Ophthalmology Department of Zagazig University Hospi-
tal, Egypt, from March 2006 to April 2008 were included in
the study. The study included only eyes with NVG and
J Glaucoma  Volume 19, Number 9, December 2010
J Glaucoma  Volume 19, Number 9, December 2010 NVG Management With PRP, IVB, and Trabeculectomy

uncontrolled IOP (>21mm Hg). Institutional review board The paired t test was used. A P value of less than 0.05
approval for the study was obtained, and an informed was considered to be statistically significant.
written consent was obtained from all patients.
A complete anterior and posterior segments examina-
tion was performed which included recording of visual RESULTS
acuity, IOP (using Goldmann applanation tonometry), Seventeen eyes of 15 patients were included in this
presence of anterior segment neovascularization, and study. The study included 11 males and 4 females. Their age
gonioscopy. The angles on gonioscopy were recorded as ranged from 44 to 74 years (mean 54.4 ± 8.5ly) (Table 1).
open, open with peripheral anterior synechiae (PAS), or There were 9 right eyes (52.9%) and 8 left eyes (47.1%).
closed. The etiology of NVG, lens status, previous ocular The causes of NVG included: diabetic retinopathy (10
surgical history, previous retinal ablation, and antiglauco- eyes), central retinal vein occlusion (5 eyes), and branch
ma medications used were also recorded. PRP was retinal vein occlusion (2 eyes). There were 12 phakic, 2
performed in either single or multiple sessions depending aphakic, and 3 pseudophakic eyes (Table 1).
on the view to the retina and patient tolerance. Medical Gonioscopy before IVB and PRP showed an open
treatment consisted of topical corticosteroid (1% pred- angle in 4 eyes (23.5%), an open angle with PAS in 5 eyes
nisolone acetate), atropine 1%, timolol maleate 0.5%, (29.4%), and a closed angle in 8 eyes (47.1%). Complete
brimonidine tartarate 0.1%, and topical or systemic
carbonic anhydrase inhibitors when tolerated. Osmotic
agents were also used occasionally on a short-term basis. TABLE 1. Patients’ Data (17 Eyes of 15 Patients)
Intravitreal injection of 1.25mg (0.05 mL) of the sterile, N (%)
undiluted, commercially available bevacizumab (Avastin; Sex
100 mg/4 mL, Genentech, Inc, South San Francisco, CA) Male 11 (73.3)
was given in the operating room through the pars plana. A Female 4 (26.7)
topical antibiotic was used 5 times daily for 1 week after Age (y)
intravitreal injection of bevacizumab. Trabeculectomy with Range 44-74
MMC was performed within 1 month after IVB injection. Mean ± SD 54.4 ± 8.5
Eye
Right 9 (52.9)
Surgical Technique Left 8 (47.1)
A fornix-based conjunctival flap was made in the Etiology of NVG
Diabetic retinopathy 10 (58.8)
superotemporal or superonasal quadrant. Traction suture
Central retinal vein occlusion 5 (29.4)
through the cornea was performed. After hemostasis of the Branch retinal vein occlusion 2 (11.8)
episcleral blood vessels with wet-field cautery, a half- Lens status
thickness rectangular scleral flap was dissected. MMC Phakic 12 (70.6)
(0.4 mg/mL) was applied over the dissected scleral bed and Aphakic 2 (11.8)
the superficial scleral flap; the conjunctivo-Tenon layers Pseudophakic 3 (17.6)
were then draped over the sponge. The free edge of the Gonioscopy (No.)
conjunctival flap was held away from the sponge so as to Open angle 4 (23.5)
avoid direct contact with MMC. After 3 minutes, the Open angle with PAS 5 (29.4)
Closed angle 8 (47.1)
sponge was removed and the entire area was thoroughly
Complete NVI regression after IVB and PRP
irrigated with balanced salt solution. A deep trabecular Incidence, No. (%) 14 (82.4)
block was removed. A cautery was applied to the iris Mean time to regression, d ( ± SD) 17.8 ± 4.8
surface before it was lifted with forceps for iridectomy to Range 8-27
avoid intraoperative bleeding. The scleral flap was closed NVI recurrence, No. (%) 5 (29.4)
with 2 interrupted 10-0 nylon sutures. The conjunctiva was Preoperative medication (No.)
closed at the limbus using interrupted 10-0 nylon sutures. Mean ± SD 2.8 ± 0.4
After surgery, all patients were treated with topical 1% Range 2-3
atropine thrice daily for 1 month, topical antibiotic Postoperative medication (No.)
Mean ± SD 0.8 ± 0.6
(Ofloxacin) for 1 to 2 weeks, and corticosteroid drops
Range 0-3
(1% prednisolone acetate) 6 times a day, tapered gradually Initial visual acuity
over a 6-week period. 1/60 or worse 7 (41.2)
Visual acuity, IOP, number of antiglaucoma medica- >1/60 to 6/60 6 (35.3)
tions, and NVI were compared before and after trabeculec- Better than 6/60 4 (23.5)
tomy. The intraoperative and postoperative complications Final visual acuity
were also recorded. All patients were examined on the first No light perception 2 (11.8)
and third postoperative day, then weekly for 1 month and 1/60 or worse 6 (35.3)
monthly for at least 6 months postoperatively. >1/60 to 6/60 4 (23.5)
Better than 6/60 5 (29.4)
The surgical outcome was defined as follows:
Success criteria
1. Complete success as IOP 21 mm Hg without anti- 1. Complete success 9 (52.9)
glaucoma medications; 2. Qualified success 6 (35.3)
2. Qualified success as IOP 21 mm Hg with antiglaucoma 3. Complete failure 2 (11.8)
medications;
IVB indicates intravitreal bevacizumab; N, number; NVG, neovascular
3. Complete failure for eyes that required further anti- glaucoma; NVI, neovascularization of iris; PAS, peripheral anterior
glaucoma surgery, developed phthisis bulbi or lost light synechiae; PRP, panretinal photocoagulation.
perception.

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Alkawas et al
TABLE 2. Mean Preoperative and Postoperative IOP in the Study
Group Along the Follow-up Period
Duration IOP (Mean ± SD)*
Before surgery 42.9 ± 4.2
First week 15.1 ± 2.2
First month 16.3 ± 2.0
Third month 18.6 ± 2.1
Sixth month 19.7 ± 2.1
*Two eyes needed cyclocryotherapy to control the IOP.
wThe matched pairs t test was used.
IOP indicates intraocular pressure.
regression of iris neovascularization (INV) after IVB and
PRP occurred in 14 eyes (82.4%). In 3 patients (17.6%),
INV was reduced but did not disappear completely. The
mean time to regression was 17.8 days ( ± 4.8 SD; range: 8
to 27ld). However, NVI recurrence was observed in 5 eyes
(29.4%; Table 1).
Mean IOP before IVB and PRP was 47.2 ± 7.7mm Hg
that decreased to 42.9 ± 4.2mm Hg within 1 month after
IVB injection.
The mean number of antiglaucoma medications used
before surgery was 2.8 ± 0.4 (range: 2 to 3). The mean
number of antiglaucoma medications used postoperatively
was 0.8 ± 0.6 (range: 0 to 3; Table 1).
Initial and final visual acuities are shown in Table 1.
Two eyes (11.8%) had lost preoperative light perception.
Complete success was observed in 9 eyes (52.9%),
whereas qualified success was found in 6 eyes (35.3%) and
complete failure was found in 2 eyes (11.8%) (Table 1).
After trabeculectomy with MMC, mean IOP was
reduced from 42.9 ± 4.2mm Hg preoperatively to
15.1 ± 2.2, 16.3 ± 2.0, 18.6 ± 2.1, and 19.7 ± 2.1mm Hg
at first week, first month, third month, and sixth month,
respectively. This reduction was statistically significant
(P<0.05) (Table 2 and Fig. 1).
Intraoperative complications included hyphema in 1
eye. It was mild and the blood was rapidly absorbed within
the first postoperative week. Postoperative complications
included: hypotony (IOP 7mm Hg) in 17.6% (3 of 17 eyes),
conjunctival dehiscence in 5.9%, shallow anterior chamber
in 11.8%, hyphema in 23.5%, and choroidal detachment in
11.8%. Hyphema was transient and disappeared within few
days. There was only 1 eye (5.9%) with epithelial corneal
erosions related to applications of MMC, but it improved
FIGURE 1. Changes in mean intraocular pressure (IOP) along the
follow-up period.
624 | www.glaucomajournal.com
J Glaucoma  Volume 19, Number 9, December 2010
TABLE 3. Postoperative Complications in the Study Group
Patients
Pw
Complications Number %
<0.05
<0.05 1. Hypotony 3 17.6
<0.05 2. Conjunctival dehiscence 1 5.9
<0.05 4. Shallow anterior 2 11.8
chamber
5. Corneal erosion 1 5.9
5. Hyphema 4 23.5
6. Choroidal detachment 2 11.8
7. Blebitis — —
8. Endophthalmitis — —
with time. Severe complications such as blebitis or
endophthalmitis did not occur during the follow-up period
(Table 3).
Of the 5 eyes with recurrent neovascularization,
additional PRP and IVB injection was performed that
resulted in regression of the neovascularization in 3 eyes. In
2 eyes persistent neovascularization was present and the
trabeculectomy was not functioning. These 2 eyes needed
cyclocryotherapy to control the IOP and these were the eyes
that lost light perception.
DISCUSSION
The key to NVG management lies in elimination of the
angiogenic stimulus before surgery by adequate PRP or
anterior retinal cryotherapy. The success of all types of
filtration surgery depends ultimately on prevention of
filtration bleb fibrosis, infection, and wound leaks.17
Before the introduction of retinal ablation therapy,
glaucoma filtering surgery in severely compromised eyes
with NVG was largely unsuccessful.1 The congested
anterior segment along with persistent NVI was the source
of severe intraoperative bleeding.2–5 With the introduction
of PRP, filtering surgery for NVG has been more
successful. Using standard filtration techniques with pre-
operative PRP, several investigators have reported im-
proved success in NVG.3,6–8 Encouraging surgical results
with the use of modified filtration surgery have been
reported in several studies with short follow-up. However,
extended follow-up data indicate that there is a high risk of
long-term failure with the loss of useful vision.6
To improve the success rate of surgery in eyes with
NVG, several modifications or adjunctive treatment are
advocated. They include application of bipolar cautery to
iris/ciliary processes exposed by iridectomy,4,5 and sub-
conjunctival 5-FU injection. This has not improved the
long-term success.7
Rubeosis can be severe, if there is a breach in the
anterior hyaloid surface (as in vitrectomy) and the posterior
capsule. The options to control the IOP are very limited.
Although conventional trabeculectomy invariably fails to
control NVG,18 augmentation with MMC or 5-FU has a
low success rate.19 Another management option is the use
of cyclodestructive procedures, but the results are unpre-
dictable and development of hypotony is a common
complication.20 This problem is particularly intense in
young patients.21
Significantly raised levels of VEGF have been demon-
strated in patients with rubeosis and NVG as well as other
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J Glaucoma  Volume 19, Number 9, December 2010
ocular neovascular diseases.22 Bevacizumab causes regres-
sion of NVI when injected into the vitreous or anterior
chamber.11,12,23–25 Yuzbasioglu et al26 studied the effects of
simultaneous intravitreal and intracameral injection of
1.25mg bevacizumab in 15 NVG cases. After treatment,
neovascularizations of iris and angle were completely
resolved 36 hours after injection in all patients.
Gupta et al27 compared the effect of 1.25 and 2.5 mg
ICB on surgical outcomes of trabeculectomy for NVG.
They found that the efficacy of an intracameral dose of
2.5 mg of bevacizumab before trabeculectomy for eyes
with NVG was not significantly different from a 1.25 mg
dose.
This study showed that complete regression of INV
after IVB and PRP occurred in 14 eyes (82.4%). In 3
patients (17.6%), INV was reduced but did not disappear
completely. The mean time to regression was 17.8 days
(± 4.8 SD; range: 8 to 27 d).
Iliev et al15 showed that IVB was followed by a
marked regression up to a complete disappearance of iris
and angle neovascularization within 48 hours in all the 6
eyes included in their study. Ehlers et al22 showed that there
was a significantly higher frequency and rate of neovascular
regression in patients treated with bevacizumab and PRP
than in patients treated with PRP alone (100% vs. 17% of
eyes and 12 d vs. 127 d, respectively). Batiolu et al28 showed
rapid improvement of retinal and INV after a single IVB
injection in a patient with central retinal vein occlusion and
NVG. About a week after IVB injection, new vessels were
no longer visible. IOP improved and additional laser
photocoagulation was performed. This also agrees with
earlier studies of treatment with bevacizumab alone that
have shown iris neovascular regression earlier than is
expected with PRP alone, suggesting that bevacizumab
plays the predominant role early on.12,22 Gheith et al29
treated 6 patients with 1.25mg (0.05 mL) of IVB followed
by PRP approximately 1 week later. In all cases, there was a
complete regression of iris and anterior chamber angle
neovascularization. Beutel et al13 evaluated the long-term
effects of intraocular bevacizumab injections as adjuvant
treatment in patients with NVG. At the last follow-up,
complete regression of rubeosis was detectable in 5 (20%)
eyes, incomplete regression in 7 (35%), stabilization in 6
(30%), and an increase in 2 (10%) eyes.
This study showed that mean IOP before IVB and
PRP was 47.2 ± 7.7 mm Hg that decreased to 42.9
± 4.2 mm Hg within 1 month after IVB injection. This is
in agreement with the results of Ehlers et al22 who showed
that the bevacizumab/PRP group had a significant reduc-
tion in IOP compared with patients treated with PRP alone
( 11 mm Hg vs. 0 mm Hg, respectively). Iliev et al15
reported a reduction of IOP in 3 out of 6 eyes after IVB for
NVG. Kitnarong et al,24 in contrast, demonstrated that
adjunctive IVB caused no IOP reduction but a rapid
regression of neovascularization of both the iris and retina
in NVG. This effect resulted in the decrease of intraopera-
tive bleeding during filtration surgery and probably
improved the surgical success. Moraczewski et al30 eval-
uated the course and outcomes of NVG treated with IVB.
The authors recommended that eyes must be monitored
closely after initial injection of IVB, regardless of initial
angle status, as many may still require surgery to lower IOP
or repeat injections of IVB. Wakabayashi et al31 also found
that the IVB is well tolerated, effectively stabilized INV
activity, and controlled IOP in patients with INV alone and
r 2010 Lippincott Williams & Wilkins
NVG Management With PRP, IVB, and Trabeculectomy
early-stage NVG without angle closure. In advanced NVG,
IVB cannot control IOP but may be used adjunctively to
improve subsequent surgical results.
In this study, a recurrence of neovascularization was
observed in 5 eyes (29.4%) (Table 1). Of the 5 eyes with
recurrent neovascularization, additional PRP and IVB
injection was performed that resulted in regression of the
neovascularization in 3 eyes. In 2 eyes persistent neovascu-
larization was present and the trabeculectomy was not
functioning. These 2 eyes needed cyclocryotherapy to
control the IOP and these were the eyes that lost light
perception. Gheith et al29 reported a recurrence of
neovascularization in 2 out of 6 eyes treated with IVB
and PRP. These patients received another IVB injection
followed by additional PRP, which resulted in the resolu-
tion of the recurrent neovascularization. Kitnarong et al24
reported that at the last follow-up all 6 eyes in their study
had benefited from IVB and trabeculectomy, with con-
trolled IOP, no symptoms, and the reduction of post-
operative antiglaucoma medication. Neither local nor
systemic side effects were reported. One patient had
recurrent NVI, which finally regressed after additional
PRP.
The effect of bevacizumab on neovascular regression
shows that VEGF plays an important role in the
pathogenesis of NVG. If intravitreal injection of bevacizu-
mab is combined with PRP, this will theoretically cause
regression of neovascularization early until the long-lasting
effect of PRP occurs.22
Adjuvant bevacizumab for NVG may offer a more
effective treatment of the neovascular trigger, might be able
to prevent further PAS formation and secondary angle
damage, and thereby may prevent the need for surgical
intervention.15,22
Even if its effect is transient, bevacizumab may have
at least an adjunctive role to PRP because of its rapid,
dramatic biologic effect. It could be of benefit in the
presence of media opacity precluding PRP. It may also act
as a surgical adjuvant as preoperative administration of
bevacizumab is shown to reduce intraoperative bleeding for
trabeculectomy or vitreoretinal surgery.28
Trabeculectomy in NVG patients usually results in
frequent intraoperative complications and poor surgical
outcomes.32 In this study, mild intraoperative bleeding
occurred in only 1 eye but postoperative hyphema
developed in 4 eyes (23.5%). It was transient and dis-
appeared within few days.
In this study, mean IOP was reduced from 42.9 ±
4.2 mm Hg preoperatively to 15.1 ± 2.2, 16.3 ± 2.0, and
19.7 ± 2.1 mm Hg at first week, first month, and sixth
month postoperatively, respectively. This reduction was
statistically significant (P<0.05) (Table 2 and Fig. 1).
Complete success was observed in 9 eyes (52.9%), whereas
qualified success was found in 6 eyes (35.3%) and complete
failure was found in 2 eyes (11.8%) (Table 1). Kitnarong
et al24 reported that 5 of 6 patients had IOP under 21 mm
Hg (range: 2 to 16 mm Hg) without medication after IVB
and PRP followed by trabeculectomy and MMC. Two
patients with central retinal vein occlusion in their study
lost their light perception; this was accounted for by the
advanced nature of the NVG and the poor prognosis of
central retinal vein occlusion itself.
Cornish et al21 reported 2 cases of young diabetic
patients with intractable NVG who were success-
fully managed with bevacizumab and MMC-augmented
www.glaucomajournal.com | 625
Alkawas et al
trabeculectomy. Iris rubeosis resolved within 48 hours.
Both patients have a follow-up period of 6 months and
the IOP remained between 10 and 15 mm Hg.
Controlling IOP due to NVG in young diabetic
patients is difficult and augmented trabeculectomy has a
very high failure rate. The addition of IVB in the
management of NVG particularly in young diabetic
patients may improve the success rate of IOP control.21
In conclusion, trabeculectomy with intraoperative
MMC after an adjunctive treatment with IVB and PRP is
a good treatment modality in the management of eyes with
NVG. It is effective in reducing NVI and intraoperative
complications during trabeculectomy.
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