Objective: To evaluate the changes in aqueous concentrations of inflammatory cytokines and fibrosis-related factors, and to detect the expression of vascular endothelial growth factor (VEGF) and proliferating cells in fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR) after injection of intravitreal bevacizumab (IVB). Methods: Forty-two eyes of 42 patients with PDR, including 28 eyes that received IVB (1.25 mg) 2, 5, and 14 days before pars plana vitrectomy (PPV), and 14 eyes without IVB, were enrolled, in addition to 10 eyes of 10 patients with nondiabetic ocular diseases. Aqueous concentrations of inflammatory cytokines and fibrosis-related factors were analyzed by a multiplex bead assay. Fluorescence immunostaining was performed to examine the expression of VEGF and proliferating cells in the excised epiretinal membranes. Results: PDR eyes without IVB had the highest vitreous VEGF levels, and the level was statistically significant compared with that of PDR eyes that received IVB 2 days before surgery, PDR eyes that received IVB 5 days before surgery, and nondiabetic eyes (p = 0.011, p = 0.012, and p < 0.001, respectively). The expression of fibroblastic cells and connective tissue growth factor increased in epiretinal FVMs of the IVB group 21 days after treatment. Conclusions: IVB injection may lead to a decrease in the intraocular concentrations of VEGF after 2–5 days and induce the formation of proliferation after 21 days, which suggests that PPV in PDR patients should take place within 1 week of the administration of preoperative IVB.

1.
Moss
SE
,
Klein
R
,
Klein
BE
.
The 14-year incidence of visual loss in a diabetic population
.
Ophthalmology
.
1998
Jun
;
105
(
6
):
998
1003
.
[PubMed]
0161-6420
2.
Miller
JW
,
Adamis
AP
,
Aiello
LP
.
Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy
.
Diabetes Metab Rev
.
1997
Mar
;
13
(
1
):
37
50
.
[PubMed]
0742-4221
3.
Ferrara
N
.
Role of vascular endothelial growth factor in regulation of physiological angiogenesis
.
Am J Physiol Cell Physiol
.
2001
Jun
;
280
(
6
):
C1358
66
.
[PubMed]
0363-6143
4.
Pandya
NM
,
Dhalla
NS
,
Santani
DD
.
Angiogenesis—a new target for future therapy
.
Vascul Pharmacol
.
2006
May
;
44
(
5
):
265
74
.
[PubMed]
1537-1891
5.
The Diabetic Retinopathy Study Research Group
.
Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8
.
Ophthalmology
.
1981
Jul
;
88
(
7
):
583
600
.
[PubMed]
0161-6420
6.
Fierson
WM
American Academy of Pediatrics Section on Ophthalmology
American Academy of Ophthalmology
American Association for Pediatric Ophthalmology and Strabismus
;
American Association of Certified Orthoptists
.
Screening examination of premature infants for retinopathy of prematurity
.
Pediatrics
.
2013
Jan
;
131
(
1
):
189
95
.
[PubMed]
0031-4005
7.
Early Treatment for Retinopathy of Prematurity Cooperative G
.
Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, Tung B, Redford M: final visual acuity results in the early treatment for retinopathy of prematurity study
.
Arch Ophthalmol
.
2010
;
128
(
6
):
663
71
. 0003-9950
8.
Gunther
JB
,
Altaweel
MM
.
Bevacizumab (Avastin) for the treatment of ocular disease
.
Surv Ophthalmol
.
2009
May-Jun
;
54
(
3
):
372
400
.
[PubMed]
0039-6257
9.
Arevalo
JF
,
Lasave
AF
,
Wu
L
,
Maia
M
,
Diaz-Llopis
M
,
Alezzandrini
AA
, et al.
Pan-American Collaborative Retina Study G: Intravitreal bevacizumab for proliferative diabetic retinopathy: Results from the pan-american collaborative retina study group (pacores) at 24 months of follow-up
.
Retina
.
2016
.0275-004X
10.
Arimura
N
,
Otsuka
H
,
Yamakiri
K
,
Sonoda
Y
,
Nakao
S
,
Noda
Y
, et al.
Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy
.
Ophthalmology
.
2009
May
;
116
(
5
):
921
6
.
[PubMed]
0161-6420
11.
Chen
E
,
Park
CH
.
Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy
.
Retina
.
2006
Jul-Aug
;
26
(
6
):
699
700
.
[PubMed]
0275-004X
12.
Ishikawa
K
,
Honda
S
,
Tsukahara
Y
,
Negi
A
.
Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy
.
Eye (Lond)
.
2009
Jan
;
23
(
1
):
108
11
.
[PubMed]
0950-222X
13.
Smith
JM
,
Steel
DH
.
Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy
.
Cochrane Database Syst Rev
.
2015
Aug
;(
8
):
CD008214
.
[PubMed]
1469-493X
14.
Zhao
LQ
,
Zhu
H
,
Zhao
PQ
,
Hu
YQ
.
A systematic review and meta-analysis of clinical outcomes of vitrectomy with or without intravitreal bevacizumab pretreatment for severe diabetic retinopathy
.
Br J Ophthalmol
.
2011
Sep
;
95
(
9
):
1216
22
.
[PubMed]
0007-1161
15.
di Lauro
R
,
De Ruggiero
P
,
di Lauro
R
,
di Lauro
MT
,
Romano
MR
.
Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefe’s archive for clinical and experimental ophthalmology =
.
Albrecht Von Graefes Arch Klin Exp Ophthalmol
.
2010
;
248
(
6
):
785
91
. 0065-6100
16.
Arevalo
JF
,
Maia
M
,
Flynn
HW
 Jr
,
Saravia
M
,
Avery
RL
,
Wu
L
, et al.
Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy
.
Br J Ophthalmol
.
2008
Feb
;
92
(
2
):
213
6
.
[PubMed]
0007-1161
17.
El-Sabagh
HA
,
Abdelghaffar
W
,
Labib
AM
,
Mateo
C
,
Hashem
TM
,
Al-Tamimi
DM
, et al.
Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: histopathologic findings and clinical implications
.
Ophthalmology
.
2011
Apr
;
118
(
4
):
636
41
.
[PubMed]
0161-6420
18.
Li
JK
,
Wei
F
,
Jin
XH
,
Dai
YM
,
Cui
HS
,
Li
YM
.
Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab
.
Int J Ophthalmol
.
2015
Dec
;
8
(
6
):
1202
6
.
[PubMed]
2222-3959
19.
Sohn
HJ
,
Han
DH
,
Kim
IT
,
Oh
IK
,
Kim
KH
,
Lee
DY
, et al.
Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema
.
Am J Ophthalmol
.
2011
Oct
;
152
(
4
):
686
94
.
[PubMed]
0002-9394
20.
Ma
Y
,
Zhang
Y
,
Zhao
T
,
Jiang
YR
:
Vascular endothelial growth factor in plasma and vitreous fluid of patients with proliferative diabetic retinopathy patients after intravitreal injection of bevacizumab.
American journal of ophthalmology
2012
;153:307-313 e302.
21.
Qian
J
,
Lu
Q
,
Tao
Y
,
Jiang
YR
.
Vitreous and plasma concentrations of apelin and vascular endothelial growth factor after intravitreal bevacizumab in eyes with proliferative diabetic retinopathy
.
Retina
.
2011
Jan
;
31
(
1
):
161
8
.
[PubMed]
1539-2864
22.
Funatsu
H
,
Yamashita
H
,
Noma
H
,
Mimura
T
,
Nakamura
S
,
Sakata
K
, et al.
Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients
.
Graefes Arch Clin Exp Ophthalmol
.
2005
Jan
;
243
(
1
):
3
8
.
[PubMed]
0721-832X
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.