0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Reduction in Dose of Intravitreous Bevacizumab Before Vitrectomy for Proliferative Diabetic Retinopathy FREE

Hidetaka Yamaji, MD; Fumio Shiraga, MD; Chieko Shiragami, MD; Hiroyuki Nomoto, MD; Tomoyoshi Fujita, MD; Kouki Fukuda, MD
[+] Author Affiliations

Author Affiliations: Department of Ophthalmology, Kagawa University Faculty of Medicine, Kagawa, Japan.


Arch Ophthalmol. 2011;129(1):106-110. doi:10.1001/archophthalmol.2010.333.
Text Size: A A A
Published online

Bevacizumab (Avastin) is a full-length recombinant humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF). It has been approved by the US Food and Drug Administration for the treatment of metastatic colorectal cancer.

Intravitreous (IV) injection of bevacizumab, 1.25 mg/0.05 mL, has been studied in patients with age-related macular degeneration, macular edema associated with retinal vein occlusion, and diabetic macular edema. Recently, bevacizumab administered prior to vitrectomy for proliferative diabetic retinopathy (PDR) was reported to reduce intraoperative bleeding.1 Sawada et al2 showed that IV bevacizumab blocked all free VEGF in the aqueous humor.

However, IV bevacizumab may cause systemic adverse effects such as thromboembolic diseases or increases in systolic blood pressure.3 Moreover, the rapid progression of traction retinal detachment after IV injection of bevacizumab was reported.4 Therefore, we need to consider an appropriate dose of bevacizumab to be injected intravitreally. The purpose of this study is to elucidate whether a reduced dose (0.25 mg) of IV bevacizumab has an effect equally strong as the widely administered dose (1.25 mg) when IV bevacizumab is used as a surgical adjunct to treat PDR.

Thirty-eight eyes of 36 diabetic patients with PDR were studied. This study of the off-label use of bevacizumab and the collection of aqueous humor before and after IV injection were approved by the institutional review board of Kagawa University Faculty of Medicine.

All patients had vitreous hemorrhage or traction foveal detachment due to PDR. All patients underwent vitrectomy after IV injection of bevacizumab. Either 1.25 mg/0.05 mL or 0.25 mg/0.01 mL of bevacizumab was injected into the vitreous as a preoperative adjunct. Twenty-four consecutive eyes were treated with IV injection of 1.25 mg of bevacizumab between October 1, 2006, and February 29, 2008, and 14 consecutive eyes were treated with IV injection of 0.25 mg of bevacizumab between March 1, 2008, and September 30, 2009. Vitrectomy was performed 1 to 5 days after the injection. An aqueous humor sample was obtained just before IV injection of bevacizumab and just before vitrectomy. The concentration of free VEGF in the aqueous humor was measured with an enzyme-linked immunosorbent assay for human VEGF (Quankine VEGF enzyme-linked immunosorbent assay kit; R&D Systems, Minneapolis, Minnesota). Results were analyzed using SPSS version 12.1 statistical software (SPSS Inc, Chicago, Illinois).

No statistically significant differences were found between the dose groups in baseline characteristics such as patient age, duration of diabetes, and presence of vitreous hemorrhage or traction foveal detachment. There were no statistically significant differences between both groups in the frequency of intraoperative hemostasis (high infusion pressure or diathermy) (1.25-mg group, 13%; 0.25-mg group, 7%) and the incidence of postoperative vitreous hemorrhage (1.25-mg group, 13%; 0.25-mg group, 14%). No local complications or systemic adverse effects were observed in all eyes.

The mean (SD) free VEGF concentration in the aqueous humor before IV injection of bevacizumab was 349.0 (255.8) pg/mL in the 0.25-mg dose group and 359.5 (231.7) pg/mL in the 1.25-mg dose group. There were no significant differences between the groups. The VEGF levels in the aqueous humor 2 to 5 days after IV injection of bevacizumab were less than the limit of detection (31.0 pg/mL) in all eyes of both groups. Fluorescein angiography was performed before and 24 hours after the 0.25-mg IV injection of bevacizumab in 3 cases. Twenty-four hours after IV injection of bevacizumab, fluorescein angiography showed dramatic regression of retinal neovascularization with marked resolution of the leakage from active neovascularization seen before the injection (Figure).

Place holder to copy figure label and caption
Figure.

Fluorescein angiograms before the intravitreous injection of 0.25 mg of bevacizumab (A) and 24 hours after the intravitreous injection of bevacizumab (B) in a 56-year-old diabetic patient with traction foveal detachment. A, Fluorescein leakage from active neovascularization was seen. B, Fluorescein leakage substantially decreased after the intravitreous injection of bevacizumab.

Graphic Jump Location

The free VEGF concentration in the aqueous humor is different from that in the vitreous. However, the VEGF level in the aqueous humor has been reported to be significantly correlated with the VEGF level in the vitreous and is correlated with the severity of diabetic retinopathy and the activity of PDR.5 Both 1.25-mg and 0.25-mg IV injections of bevacizumab blocked all free VEGF in the aqueous humor. Nevertheless, 1.25 mg has been widely administered as the standard dose of IV bevacizumab. This study suggests that a lower dose (0.25 mg) of IV bevacizumab may be effective as a preoperative adjunct before vitrectomy in the treatment of PDR.

ARTICLE INFORMATION

Correspondence: Dr Yamaji, Department of Ophthalmology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan (proceed@kms.ac.jp).

Financial Disclosure: None reported.

Chen  EPark  CH Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina 2006;26 (6) 699- 700
PubMed Link to Article
Sawada  OKawamura  HKakinoki  MSawada  TOhji  M Vascular endothelial growth factor in aqueous humor before and after intravitreal injection of bevacizumab in eyes with diabetic retinopathy. Arch Ophthalmol 2007;125 (10) 1363- 1366
PubMed Link to Article
Shima  CSakaguchi  HGomi  F  et al.  Complications in patients after intravitreal injection of bevacizumab. Acta Ophthalmol 2008;86 (4) 372- 376
PubMed Link to Article
Oshima  YShima  CWakabayashi  T  et al.  Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment. Ophthalmology 2009;116 (5) 927- 938
PubMed Link to Article
Funatsu  HYamashita  HNoma  H  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;243 (1) 3- 8
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Fluorescein angiograms before the intravitreous injection of 0.25 mg of bevacizumab (A) and 24 hours after the intravitreous injection of bevacizumab (B) in a 56-year-old diabetic patient with traction foveal detachment. A, Fluorescein leakage from active neovascularization was seen. B, Fluorescein leakage substantially decreased after the intravitreous injection of bevacizumab.

Graphic Jump Location

Tables

References

Chen  EPark  CH Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina 2006;26 (6) 699- 700
PubMed Link to Article
Sawada  OKawamura  HKakinoki  MSawada  TOhji  M Vascular endothelial growth factor in aqueous humor before and after intravitreal injection of bevacizumab in eyes with diabetic retinopathy. Arch Ophthalmol 2007;125 (10) 1363- 1366
PubMed Link to Article
Shima  CSakaguchi  HGomi  F  et al.  Complications in patients after intravitreal injection of bevacizumab. Acta Ophthalmol 2008;86 (4) 372- 376
PubMed Link to Article
Oshima  YShima  CWakabayashi  T  et al.  Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment. Ophthalmology 2009;116 (5) 927- 938
PubMed Link to Article
Funatsu  HYamashita  HNoma  H  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;243 (1) 3- 8
PubMed Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

644 Views
3 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs