Purpose: The current body of evidence on the efficacy and safety of anti-VEGFs for macular oedema secondary to branch retinal vein occlusion (BRVO) is steadily growing as large clinical trials and observational studies are continually completed. The aim of this meta-analysis is to analyse anatomical and functional outcomes in response to anti-VEGF therapy using evidence generated from a pooled analysis of current clinical trials and observational studies. Methods: The current meta-analysis includes treatment of BRVO with aflibercept, bevacizumab and ranibizumab from randomised controlled trials and observational studies. Inclusion criteria included peer-reviewed publications with at least a 12-month follow-up period. On literature review using multiple electronic databases (PubMed, Embase and Cochrane), 22 studies met the inclusion criteria. Baseline patient characteristics, study design, sample size and 12- and 24-month change in best corrected visual acuity (BCVA) and central foveal thickness (CFT) as measured on optical coherence tomography imaging were pooled in a meta-analysis. Data were then stratified by study design and anti-VEGF therapy in subgroup analyses. Results: A total of 1,236 eyes from 22 studies were included in this meta-analysis. Mean baseline BCVA ranged from 66 ETDRS letters (20/50 Snellen equivalent) to 35 letters (20/200 Snellen). Mean baseline CFT ranged from 406.0 to 681.0 µm. Anti-VEGF treatment demonstrated an overall mean improvement in BCVA at 12 months of 14 letters (95% CI 12.0 to 16.2, p < 0.001) and CFT reduction of 228 µm (95% CI –278.9 to –176.1, p < 0.001). The BCVA gains at 12 months were maintained to month 24 with a mean gain of 12.5 letters (95% CI 6.3 to 18.8, p < 0.001), as well as reduction of CFT of 238 µm (95% CI –336.0 to –140.2, p < 0.001). No cases of endophthalmitis or glaucoma were reported in any study. Conclusion: This meta-analysis confirms the comparable safety and efficacy of anti-VEGF therapies for patients with cystoid macular oedema secondary to BRVO. There is a need for randomised prospective comparative trials of anti-VEGF agents for BRVO.

1.
Rogers
S
,
McIntosh
RL
,
Cheung
N
,
Lim
L
,
Wang
JJ
,
Mitchell
P
, et al.;
International Eye Disease Consortium
.
The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia
.
Ophthalmology
.
2010
Feb
;
117
(
2
):
313
9.e1
.
[PubMed]
0161-6420
2.
Rogers
SL
,
McIntosh
RL
,
Lim
L
,
Mitchell
P
,
Cheung
N
,
Kowalski
JW
, et al.
Natural history of branch retinal vein occlusion: an evidence-based systematic review
.
Ophthalmology
.
2010
Jun
;
117
(
6
):
1094
1101.e5
.
[PubMed]
0161-6420
3.
Fraenkl
SA
,
Mozaffarieh
M
,
Flammer
J
.
Retinal vein occlusions: the potential impact of a dysregulation of the retinal veins
.
EPMA J
.
2010
Jun
;
1
(
2
):
253
61
.
[PubMed]
1878-5077
4.
Noma
H
,
Funatsu
H
,
Mimura
T
.
Association of electroretinographic parameters and inflammatory factors in branch retinal vein occlusion with macular oedema
.
Br J Ophthalmol
.
2012
Dec
;
96
(
12
):
1489
93
.
[PubMed]
0007-1161
5.
Yoshimura
T
,
Sonoda
KH
,
Sugahara
M
,
Mochizuki
Y
,
Enaida
H
,
Oshima
Y
, et al.
Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases
.
PLoS One
.
2009
Dec
;
4
(
12
):
e8158
.
[PubMed]
1932-6203
6.
Noma
H
,
Funatsu
H
,
Yamasaki
M
,
Tsukamoto
H
,
Mimura
T
,
Sone
T
, et al.
Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6
.
Am J Ophthalmol
.
2005
Aug
;
140
(
2
):
256
61
.
[PubMed]
0002-9394
7.
Noma
H
,
Funatsu
H
,
Mimura
T
,
Eguchi
S
,
Hori
S
.
Soluble vascular endothelial growth factor receptor-2 and inflammatory factors in macular edema with branch retinal vein occlusion
.
Am J Ophthalmol
.
2011
Oct
;
152
(
4
):
669
677.e1
.
[PubMed]
0002-9394
8.
Karia
N
.
Retinal vein occlusion: pathophysiology and treatment options
.
Clin Ophthalmol
.
2010
Jul
;
4
:
809
16
.
[PubMed]
1177-5467
9.
Kern
TS
.
Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy
.
Exp Diabetes Res
.
2007
;
2007
:
95103
.
[PubMed]
1687-5214
10.
Rhoades
W
,
Dickson
D
,
Nguyen
QD
,
Do
DV
.
Management of macular edema due to central retinal vein occlusion - The role of aflibercept
.
Taiwan J Ophthalmol
.
2017
Apr-Jun
;
7
(
2
):
70
6
.
[PubMed]
2211-5056
11.
Pai
SA
,
Shetty
R
,
Vijayan
PB
,
Venkatasubramaniam
G
,
Yadav
NK
,
Shetty
BK
, et al.
Clinical, anatomic, and electrophysiologic evaluation following intravitreal bevacizumab for macular edema in retinal vein occlusion
.
Am J Ophthalmol
.
2007
Apr
;
143
(
4
):
601
6
.
[PubMed]
0002-9394
12.
Campochiaro
PA
,
Hafiz
G
,
Shah
SM
,
Nguyen
QD
,
Ying
H
,
Do
DV
,
Quinlan
E
,
Zimmer-Galler
I
,
Haller
JA
,
Solomon
SD
,
Sung
JU
,
Hadi
Y
,
Janjua
KA
,
Jawed
N
,
Choy
DF
,
Arron
JR
:
Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator.
Molecular therapy : the journal of the American Society of Gene Therapy
2008
;16:791-799.
13.
Downs
SH
,
Black
N
.
The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions
.
J Epidemiol Community Health
.
1998
Jun
;
52
(
6
):
377
84
.
[PubMed]
0143-005X
14.
Higgins
JP
,
Thompson
SG
,
Deeks
JJ
,
Altman
DG
.
Measuring inconsistency in meta-analyses
.
BMJ
.
2003
Sep
;
327
(
7414
):
557
60
.
[PubMed]
0959-8138
15.
Higgins
JP
,
Thompson
SG
.
Quantifying heterogeneity in a meta-analysis
.
Stat Med
.
2002
Jun
;
21
(
11
):
1539
58
.
[PubMed]
0277-6715
16.
Clark
WL
,
Boyer
DS
,
Heier
JS
,
Brown
DM
,
Haller
JA
,
Vitti
R
, et al.
Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study
.
Ophthalmology
.
2016
Feb
;
123
(
2
):
330
6
.
[PubMed]
0161-6420
17.
Pichi
F
,
Elbarky
AM
,
Elhamaky
TR
.
Outcome of “treat and monitor” regimen of aflibercept and ranibizumab in macular edema secondary to non-ischemic branch retinal vein occlusion
.
Int Ophthalmol
.
2017
.
[PubMed]
0165-5701
18.
Wang
JK
,
Su
PY
,
Hsu
YR
,
Chen
YJ
,
Chen
FT
,
Tseng
YY
.
Comparison of the Efficacy of Intravitreal Aflibercept and Bevacizumab for Macular Edema Secondary to Branch Retinal Vein Occlusion
.
J Ophthalmol
.
2016
;
2016
:
8421940
.
[PubMed]
2090-004X
19.
Bandello
F
,
Augustin
A
,
Tufail
A
,
Leaback
R
.
A 12-month, multicenter, parallel group comparison of dexamethasone intravitreal implant versus ranibizumab in branch retinal vein occlusion
.
Eur J Ophthalmol
.
2018
Nov
;
28
(
6
):
697
705
.
[PubMed]
1120-6721
20.
Brynskov
T
,
Kemp
H
,
Sørensen
TL
.
Intravitreal ranibizumab for retinal vein occlusion through 1 year in clinical practice
.
Retina
.
2014
Aug
;
34
(
8
):
1637
43
.
[PubMed]
0275-004X
21.
Chatziralli
I
,
Theodossiadis
G
,
Chatzirallis
A
,
Parikakis
E
,
Mitropoulos
P
,
Theodossiadis
P
.
RANIBIZUMAB FOR RETINAL VEIN OCCLUSION: Predictive Factors and Long-Term Outcomes in Real-Life Data
.
Retina
.
2018
Mar
;
38
(
3
):
559
68
.
[PubMed]
0275-004X
22.
Khan
M
,
Wai
KM
,
Silva
FQ
,
Srivastava
S
,
Ehlers
JP
,
Rachitskaya
A
, et al.
Comparison of Ranibizumab and Bevacizumab for Macular Edema Secondary to Retinal Vein Occlusions in Routine Clinical Practice
.
Ophthalmic Surg Lasers Imaging Retina
.
2017
Jun
;
48
(
6
):
465
72
.
[PubMed]
2325-8160
23.
Rezar
S
,
Eibenberger
K
,
Bühl
W
,
Georgopoulos
M
,
Schmidt-Erfurth
U
,
Sacu
S
;
Macula Study Group Vienna
.
Anti-VEGF treatment in branch retinal vein occlusion: a real-world experience over 4 years
.
Acta Ophthalmol
.
2015
Dec
;
93
(
8
):
719
25
.
[PubMed]
1755-375X
24.
Sakanishi
Y
,
Lee
A
,
Usui-Ouchi
A
,
Ito
R
,
Ebihara
N
.
Twelve-month outcomes in patients with retinal vein occlusion treated with low-frequency intravitreal ranibizumab
.
Clin Ophthalmol
.
2016
Jun
;
10
:
1161
5
.
[PubMed]
1177-5467
25.
Shiono
A
,
Kogo
J
,
Sasaki
H
,
Yomoda
R
,
Jujo
T
,
Tokuda
N
, et al.
Optical coherence tomography findings as a predictor of clinical course in patients with branch retinal vein occlusion treated with ranibizumab
.
PLoS One
.
2018
Jun
;
13
(
6
):
e0199552
.
[PubMed]
1932-6203
26.
Tan
MH
,
McAllister
IL
,
Gillies
ME
,
Verma
N
,
Banerjee
G
,
Smithies
LA
, et al.
Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion
.
Am J Ophthalmol
.
2014
Jan
;
157
(
1
):
237
247.e1
.
[PubMed]
0002-9394
27.
Ivanovska Adjievska
B
,
Boskurt
S
,
Orovcanec
N
,
Dimovska-Jordanova
V
.
The outcome of low-frequency intravitreal bevacizumab therapy for macular edema in retinal vein occlusions
.
Clin Ophthalmol
.
2017
Jun
;
11
:
1183
90
.
[PubMed]
1177-5467
28.
Gokce
G
,
Sobaci
G
,
Durukan
AH
,
Erdurman
FC
.
The comparison of intravitreal triamcinolone and bevacizumab in patients with macular edema secondary to branch retinal vein occlusion
.
Clin Ophthalmol
.
2014
Feb
;
8
:
355
62
.
[PubMed]
1177-5467
29.
Chatziralli
IP
,
Sergentanis
TN
,
Sivaprasad
S
.
HYPERREFLECTIVE FOCI AS AN INDEPENDENT VISUAL OUTCOME PREDICTOR IN MACULAR EDEMA DUE TO RETINAL VASCULAR DISEASES TREATED WITH INTRAVITREAL DEXAMETHASONE OR RANIBIZUMAB
.
Retina
.
2016
Dec
;
36
(
12
):
2319
28
.
[PubMed]
0275-004X
30.
Hikichi
T
,
Higuchi
M
,
Matsushita
T
,
Kosaka
S
,
Matsushita
R
,
Takami
K
, et al.
Two-year outcomes of intravitreal bevacizumab therapy for macular oedema secondary to branch retinal vein occlusion
.
Br J Ophthalmol
.
2014
Feb
;
98
(
2
):
195
9
.
[PubMed]
0007-1161
31.
Khan
MA
,
Mallika
V
,
Joshi
D
.
Comparison of immediate versus deferred intravitreal Bevacizumab in macular oedema due to branch retinal vein occlusion: a pilot study
.
Int Ophthalmol
.
2018
Jun
;
38
(
3
):
943
9
.
[PubMed]
0165-5701
32.
Kim
M
,
Lee
DH
,
Byeon
SH
,
Koh
HJ
,
Kim
SS
,
Lee
SC
.
Comparison of intravitreal bevacizumab and dexamethasone implant for the treatment of macula oedema associated with branch retinal vein occlusion
.
Br J Ophthalmol
.
2015
Sep
;
99
(
9
):
1271
6
.
[PubMed]
0007-1161
33.
Kornhauser
T
,
Schwartz
R
,
Goldstein
M
,
Neudorfer
M
,
Loewenstein
A
,
Barak
A
.
Bevacizumab treatment of macular edema in CRVO and BRVO: long-term follow-up. (BERVOLT study: Bevacizumab for RVO long-term follow-up)
.
Graefes Arch Clin Exp Ophthalmol
.
2016
May
;
254
(
5
):
835
44
.
[PubMed]
0721-832X
34.
Loukianou
E
,
Brouzas
D
,
Chatzistefanou
K
,
Koutsandrea
C
.
Clinical, anatomical, and electrophysiological assessments of the central retina following intravitreal bevacizumab for macular edema secondary to retinal vein occlusion
.
Int Ophthalmol
.
2016
Feb
;
36
(
1
):
21
36
.
[PubMed]
0165-5701
35.
Papadia
M
,
Misteli
M
,
Jeannin
B
,
Herbort
CP
.
The influence of anti-VEGF therapy on present day management of macular edema due to BRVO and CRVO: a longitudinal analysis on visual function, injection time interval and complications
.
Int Ophthalmol
.
2014
Dec
;
34
(
6
):
1193
201
.
[PubMed]
0165-5701
36.
Rush
RB
,
Simunovic
MP
,
Aragon
AV
 2nd
,
Ysasaga
JE
.
Treat-and-extend intravitreal bevacizumab for branch retinal vein occlusion
.
Ophthalmic Surg Lasers Imaging Retina
.
2014
May-Jun
;
45
(
3
):
212
6
.
[PubMed]
2325-8160
37.
Tsagkataki
M
,
Papathomas
T
,
Lythgoe
D
,
Kamal
A
.
Twenty-Four-Month Results of Intravitreal Bevacizumab in Macular Edema Secondary to Branch Retinal Vein Occlusion
.
Semin Ophthalmol
.
2015
;
30
(
5-6
):
352
9
.
[PubMed]
0882-0538
38.
Tilgner
E
,
Dalcegio Favretto
M
,
Tuisl
M
,
Wiedemann
P
,
Rehak
M
.
Macular cystic changes as predictive factor for the recurrence of macular oedema in branch retinal vein occlusion
.
Acta Ophthalmol
.
2017
Nov
;
95
(
7
):
e592
6
.
[PubMed]
1755-375X
39.
Genentech: FDA approves Lucentis (ranibizumab injection) for the treatment of macular edema following retinal vein occlusion.
2010
40.
Regeneron: REGENERON ANNOUNCES FDA APPROVAL OF EYLEA® (AFLIBERCEPT) INJECTION FOR MACULAR EDEMA FOLLOWING CENTRAL RETINAL VEIN OCCLUSION.
2012
41.
Dascalu
AM
,
Popa-Cherecheanu
A
,
Popa-Cherecheanu
M
,
Nica
A
,
Serban
D
.
“Off-label” use of intravitreal bevacizumab in non-ischemic macular edema secondary to retinal vein obstructions
.
Rom J Ophthalmol
.
2016
Apr-Jun
;
60
(
2
):
90
5
.
[PubMed]
2457-4325
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