Intravitreal
Bevacizumab, Triamcinolone Acetonide or Combined Treatment for Macular Edema Secondary to Branch
Retinal Vein Occlusion
Sameh
Mohamed Elgouhary, Hatem Mohamed Marey, Hoda Mohamed Elsobky, Esraa Samy
Elghobashy
Sameh
Mohamed Elgouhary, Hatem Mohamed Marey, Hoda Mohamed Elsobky, Esraa Samy
Elghobashy, Department of Ophthalmology, Menoufia
University, Egypt
Correspondence to: Sameh Mohamed Elgouhary, MD, Department of
ophthalmology, Menoufia University, Shebin Elkom, Egypt
Email: sameh_elgouhary@yahoo.com
Telephone: +2-01005543214
Received: March 22,
2015
Revised: April 28, 2015
Accepted: May 1, 2015
Published online: June 1, 2015
ABSTRACT
AIM: To evaluate the safety and efficacy
of intravitreal injection of bevacizumab (IVB), triamcinolone acetonide (IVTA)
or combined treatment (IVB+IVTA) for macular edema secondary to branch retinal
vein occlusion (BRVO).
Methods: A prospective
randomized interventional study on cases of BRVO. Fifty five eyes of 54
patients were included and divided into 3 groups. Group 1 included 20 eyes
received IVB 2.5 mg/0.1 mL. Group 2 included 18 eyes received IVTA 4 mg/0.1 ml.
Group 3 included 17 eyes received combined IVB 1.25 mg/0.05 ml and IVTA 2
mg/0.05ml. Central macular thickness (CMT) by optical coherence tomography
(OCT), visual acuity (VA), intraocular pressure (IOP), number of injections and
complications after injection were the main outcomes.
Results: Central macular
thickness is significantly reduced after injection in the 1st, 3rd and 6th
month within the same group in the three groups (P<0.001). There was
significant VA improvement in the 1st, 3rd and 6th month after injection when
compared to baseline VA within the same group in the three groups. There was
significant IOP elevation in group 2 when compared to groups 1 and 3 in the 1st
week (p=0.02), 1st month (p<0.001), 3rd month (p<0.001)
and 6th month (p<0.001) after injection. Sixty five percent of eyes required
more than one injection in group 1 compared to 16.7% in group 2 and 17.6% in
group 3.
Conclusions: The three lines;
IVB, IVTA and IVB+IVTA resulted in reduction of CMT and improvement of VA at
all follow up visits. IVTA led to the best reduction in CMT but was associated
with cataract and glaucoma formation. IVA led to the best VA but had the
highest number of injections.
© 2015 ACT. All
rights reserved.
Key words: Branch retinal vein occlusion; Bevacizumab;
Triamcinolone acetonide; Macular edema; Central macular thickness
Elgouhary SM, Marey HM, Elsobky HM, Elghobashy ES. Intravitreal
Bevacizumab, Triamcinolone Acetonide or Combined Treatment for Macular Edema
Secondary to Branch Retinal Vein Occlusion. International
Journal of Ophthalmic Research 2015; 1(1): 24-27 Available from: URL:
http://www.ghrnet.org/index.php/ijor/article/view/1128
INTRODUCTION
Branch retinal vein occlusion (BRVO) is the second most common major
retinal vascular disease after diabetic retinopathy[1]. With macular
edema is the most significant cause of central visual loss.
Treatment of
BRVO has been centered on the management of macular edema. The Branch Vein
Occlusion Study in 1984 reported that: grid laser photocoagulation of the
edematous macula results in signi¬ficant improvement of macular edema and
visual acuity compared to observation. At 3 years, 65% of treated eyes gained
at least two lines of vision versus 37% in the untreated control group[2].
Recently there have been increasing data encouraging the intravitreal
injection of anti-vascular endothelial growth factor (VEGF) substances for
macular edema associated with BRVO. Triamcinolone acetonide and bevacizumab are
the two popular drugs increasingly being used for this purpose[3-5].
The rationale
for use of an intravitreally injected anti-VEGF drug to treat BRVO is that
vascular occlusion induces up regulation of VEGF, resulting in increased
vascular permeability and subsequent macular edema[6].
The aim of
this study was to evaluate the safety and efficacy of intravitreal injection of
bevacizumab, triamcinolone acetonide or combined bevacizumab and triamcinolone
acetonide for macular edema secondary to BRVO.
method
This is a prospective randomized interventional study on 55 eyes of 54
patients with macular edema secondary to BRVO attending at the outpatient
clinic of Ophthalmology Department of Menoufia University Hospital.
All included
patients underwent best corrected visual acuity (VA) assessment using LogMar
units, anterior segment examination using slit lamp, intraocular pressure using
Goldmann applanation tonometer, posterior segment examination using slit lamp
biomicroscopy with +90 and +78 diopters volk lens. Fundus fluorescein
angiography (FFA) and Optical coherence tomography (OCT) were done at base
line, 1 month, 3 months, and 6 months after injection.
Exclusion
criteria were: (1) macular edema due to causes other than RVO as diabetic
retinopathy, retinal telangiectasia, retinal macro aneurysm; (2) previous focal
or grid macular laser photocoagulation; (3) history of cataract extraction
within 6 months before injection (to exclude Irvin- Gass syndrome); and (4) any
pathology that may interfere with assessment of VA improvement as dense
cataract, glaucoma, and high myopia.
Studied eyes
were divided into 3 groups. Group 1 included 20 eyes received intravitreal
injection of bevacizumab 2.5 mg/0.1 mL (Avastin 25 mg/mL; Genentech, San
Francisco, CA, USA). Group 2 included 18 eyes received intravitreal injection
of triamcinolone acetonide 4 mg/0.1 mL (Kenacort-A 40 mg/mL; Bristol-Myers,
Squibb). Group 3 included 17 eyes received combined bevacizumab 1.25 mg/0.05 mL
and triamcinolone acetonide 2 mg/0.05mL, all treatment lines were the first
line therapy for these patients.
After
discussing the nature of surgery with the patients including the potential
risks and complications, all patients signed a written informed consent. This
study was approved the clinical research committee of the Menoufia University
Hospital and it followed the tenets of the Declaration of Helsinki.
The technique
of injection was carried out under complete aseptic conditions in the operative
theatre with topical anesthetic eye drops (benoxinate hydrochloride 0.4%).
Paracentesis was done in all eyes at the end of the procedure to lower the
intraocular pressure (IOP) to avoid vitreous incarceration and to avoid
extrusion of some of the injected material into the track of injection.
Fluoroquinolone eye drops were instilled before (every 5 minutes for 15
minutes) and after injection (five times daily for 1 week).
All data were
expressed as mean ± standard deviations. The Kruskal-Willis test was used to
perform statistical comparisons among the three groups. Analyses were achieved
using SPSS version 14.1 (SPSS Inc., Chicago, IL, USA). P value of less than
0.05 was considered to be statistically significant.
RESULTS
Patients' data
There were 11 males and 8 females in group 1, 10 males and 8 females in
group 2 and 9 males and 8 females in group 3.The age range in years was
52.5±11.7 in group1, 55.5±8.9 in group 2 and 52.9±9.5 in group 3. There was no
statistically significant difference between the three groups regarding age (p=0.58),
gender (p=0.91), duration of BRVO (p=0.43), baseline VA (p=0.87),
baseline CMT (p=0.13) and baseline IOP (=0.34) as shown in table 1.
Central macular
thickness
Central macular thickness was significantly reduced after injection in
the 1st, 3rd and 6th month within the same group in the three groups (p<0.001).
It was significantly reduced in group 2 (IVTA) when compared to groups 1 and 3
in the 1st (p<0.001), 3rd (p=0.02), and
6th month (p=0.02) after injection.
Visual acuity
improvement
There was significant VA improvement in the 1st, 3rd
and 6th month after injection when compared to baseline VA within the same
group in the three groups. In the 1st month, there was no significant
difference between the three groups regarding VA improvement. In the 3rd
and 6th month, there was significant VA improvement in group 1 when
compared to groups 2 and 3.
Intraocular
pressure
There was no significant change in IOP when compared to baseline IOP
during the 6 months follow up in group 1. In group 2, there was significant IOP
elevation in the 1st, 3rd and 6th month after injection
when compared to baseline IOP. In group 3, there was significant IOP elevation
in the 3rd and 6th month after injection. There was
significant IOP elevation in group 2 when compared to groups 1 and 3 in the 1st
week (p=0.02), 1st month (p<0.001), 3rd month (p<0.001)
and 6th month (p<0.001) after injection.
Retreatment
Retreatment was done when CMT exceeded 300 microns one month after
injection. Sixty five percent of eyes in group 1 required more than one
injection (range, 1-3) compared to 16.7% in group 2 (range, 1-3) and 17.6% in
group 3 (range, 1-2) as shown in table 2.
Complications
Glaucoma (increased IOP more than 21 mmHg) occurred in two eyes (10%)
in group 1, six eyes (33.3%) in group 2, and three eyes (17.6%) in group 3. In
all eyes, IOP was controlled by anti-glaucoma medications, with no need for
surgical intervention.
Cataract
progressed in two eyes (out of 17 phakic eyes (11.7%)) in group 1, five eyes
(out of 15 phakic eyes (33.3%)) in group 2, and in three eyes (out of 12 phakic
eyes (25%)) in group 3 as shown in table 3.
Discussion
There are many treatment options for macular edema secondary to retinal
vein occlusion. The first is macular laser photocoagulation alone. The second
is intravitreal injection of anti-VEGF agents as bevacizumab or triamcinolone
or combined treatment. The third is combined intravitreal injection of
anti-VEGF agents followed by macular laser photocoagulation. Which option is
the best? A question still needs an answer.
In this study,
we tried to evaluate the second treatment option which is the intravitreal
injection of anti-VEGF agents, where we evaluated the safety and efficacy of
intravitreal injection of bevacizumab, triamcinolone acetonide and combined
IVB+IVTA.
All three
types of treatment resulted in significant reduction of CMT during the 6 months
of follow up. However, CMT was significantly reduced in group 2 (IVTA) when
compared to groups 1 and 3 in the 1st (p<0.001), 3rd (p=0.02)
and 6th month (p=0.02) after injection. This may be explained by the
fact that pathogenesis of macular edema in BRVO had two components. First, vein
occlusion results in increase in venous and capillary hydrostatic pressure
which results in water flux from the vessel into the tissue according to
Starling’s law. Second, hypoxia induced by vein occlusion stimulates the
expression of VEGF which induces the vascular permeability and new vessel
formation[7,8]. IVTA addresses the two components as it has a strong
anti-edematous effect (by decreasing the vascular leakage) and also it has
anti-VEGF effect while IVB addresses mainly the second component.
This
improvement in CMT in all groups were also showed in the study of Çekiç et
al[9], where significant reduction in CMT was documented in the
three treatment groups; triamcinolone, bevacizumab, and a combination of
triamcinolone-bevacizumab (p=0.02, p=0.02, and p=0.001,
respectively) after one month, and (p=0.02, p=0.02, and p=0.04,
respectively) after 6 months of treatment.
In this series, there was
significant VA improvement in the 3 groups during the 6 months of follow up
when compared to baseline VA, however VA improvement was statistically
significant in group 1 when compared to groups 2 and 3 in the 3rd
and 6th months after injection. This may be explained by the
occurrence of cataract and glaucoma related to triamcinolone injection in
groups 2 and 3. These results correlates with the work of Çekiç et al[9]
where they concluded that all treatment groups had similar therapeutic effects
at one month (p=0.02, p=0.02 and p=0.02, respectively),
but at six months, the IVB group had better visual acuity (p=0.01). In
another study of Lee et al[10],
there was statistically significant difference in the post treatment compared to
the pre treatment results at 1, 6 months, with no statistically significant
difference among the three groups at 1, 3, 6, or 24 months postoperatively.
However, at the 12-month follow-up, the IVTA group showed less visual
improve¬ment than did the other groups. Results of different anti-VEGF are
summarized in table 4.
The idea of combined injection of IVB+IVTA had many advantages: (1)
addressing the two components of pathogenesis of macular edema in BRVO equally;
(2) decreasing the dose of IVB from 2.5 mg to 1.25 mg which may decrease the
incidence of thromboembolic events; (3) decreasing the dose of IVTA from 4mg to
2mg which may decrease the incidence of cataract and glaucoma. In this study;
the incidence of cataract had decreased from 33.3% in group 2 to 25% in group
3, and the incidence of glaucoma had decreased from 33.3% in group 2 to 17.6%
in group 3. Cataract progression, and IOP elevation were also noted in the
results of Çekiç et al[9], where regarding cataract; 5 of 14
phakic eyes (36%) in Group 1 (IVTA), in 1 of 12 phakic eyes in Group 2 (IVB)
(8%), and in 2 of 20 phakic eyes in Group 3 (combined treatment) (10%) showed
cataract progression, and regarding glaucoma; two eyes had transiently elevated
intraocular pressure within the first week in Group 1 (IVTA). None of the
patients exceeded intraocular pressure value of 21 mmHg after one month.
Intraocular pressures in Group 2 (IVB) and Group 3 (combined treatment) were
less than 21 mmHg during study period. Cataract progression was also reported
with intravitreal triamcinolone[11,12], but not with intravitreal
bevacizumab injection; (4) decreasing the number of injections per eye. In this
study, the percent of eyes required more than one injection had decreased from
65% in group 1 to 17.6% in group 3. This was also noted in the study of Çekiç et
al[9], where the mean number of injections per eye within six
months were 1.4 (range 1 to 2) in Group 1 (IVTA), 1.6 (range 1 to 3) in Group 2
(IVB), and 1.4 (range 1 to 2) in Group 3 (combined treatment).
There were some limitations in this study: (1) relatively small number
of enrolled eyes; (2) short period of follow up; (3) we did not compare the
results of intravitreal injection of anti-VEGF drugs with a group of eyes
treated with macular laser photocoagulation alone; (4) we did not study the
effect of adding macular laser photocoagulation after intravitreal injection on
decreasing the frequency of injection. All these points may be a good material
for further research.
ACKNOWLEDGMENTS
The study was performed at Menoufia University Hospital. This work was
self-funded by the authors.
CONFLICT OF INTERESTS
The author has no conflicts of interest to declare.
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Peer reviewer: Do-Gyun Kim, Associate
professor, Myong-Ji Hospital, Department of Ophthalmology, 697-24,
Hwajung-dong,Deokyang-gu, Goyang-si, Gyeonggi-do, Postal code : 412-270, Korea.
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