Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

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Abstract

Purpose

To report a case of proliferative diabetic retinopathy (PDR) showing transient macular edema (ME) and deteriorated retinal function after intravitreal bevacizumab injection (IVB).

Methods and Results

A 53-year-old man received IVB (1.25 mg/0.05 ml) in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+) in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG) revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye.

Conclusion

We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

Related collections

Most cited references 10

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The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide.

A Fung, P J Rosenfeld, E Reichel (2006)

Off-label intravitreal injections of bevacizumab (Avastin) have been given for the treatment of neovascular and exudative ocular diseases since May 2005. Since then, the use of intravitreal bevacizumab has spread worldwide, but the drug-related adverse events associated with its use have been reported only in a few retrospective reviews. The International Intravitreal Bevacizumab Safety Survey was initiated to gather timely information regarding adverse events from doctors around the world via the internet. An internet-based survey was designed to identify adverse events associated with intravitreal bevacizumab treatment. The survey web address was disseminated to the international vitreoretinal community via email. Rates of adverse events were calculated from participant responses. 70 centres from 12 countries reported on 7113 injections given to 5228 patients. Doctor-reported adverse events included corneal abrasion, lens injury, endophthalmitis, retinal detachment, inflammation or uveitis, cataract progression, acute vision loss, central retinal artery occlusion, subretinal haemorrhage, retinal pigment epithelium tears, blood pressure elevation, transient ischaemic attack, cerebrovascular accident and death. None of the adverse event rates exceeded 0.21%. Intravitreal bevacizumab is being used globally for ocular diseases. Self-reporting of adverse events after intravitreal bevacizumab injections did not show an increased rate of potential drug-related ocular or systemic events. These short-term results suggest that intravitreal bevacizumab seems to be safe.

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Penetration of bevacizumab through the retina after intravitreal injection in the monkey.

Focke Ziemssen, Sigrid Schultheiss, Ulrich Schraermeyer … (2007)

The penetration of intravitreally injected bevacizumab in its commercial formulation (Avastin; Roche, Grenzach, Germany) through the retina was studied, to determine whether a full-length antibody would be able to penetrate the retina as easily as an antibody fragment. Six cynomolgus monkeys (Macaca fascicularis) were used in this study. Two compositions of intravitreal injection into the right eyes were performed: one with commercial Avastin (group 1, four animals) and the other one with commercial Avastin labeled with 125I (group 2, one animal). The animals in group 1 were killed 1, 4, 7, or 14 days after the injection for subsequent histologic analysis of the eyes by immunohistochemistry, and the animal in group 2 was killed 7 days after injection for autoradiography and electron microscopy. Funduscopy was performed before the injection and at several time points thereafter. Moreover, blood samples were collected at different time points from the group-2 animal. The sixth animal remained untreated and served as the control. No pathologic changes were obvious in the funduscopic images within the time of the experiment. Bevacizumab immunoreactivity was found in the choroid and the inner layers of the retina as early as 1 day after the injection and spread to the outer layers and the choroid within the following days, in particular to photoreceptors and blood vessels. Avastin labeled with 125I showed radioactivity in blood serum 1 day after the intravitreal injection and remained relatively stable until day 7. The results clearly show that the bevacizumab molecule can penetrate the retina and is also transported into the retinal pigment epithelium, the choroid and, in particular, into photoreceptor outer segments after intravitreal injection of Avastin. Active transport mechanisms seem to be involved.

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Ultrastructural findings in the primate eye after intravitreal injection of bevacizumab.

, Krista K Bartz, Focke Ziemssen … (2007)

To examine the ultrastructural effect of intravitreal bevacizumab on primate eyes with particular focus set on the choriocapillaris and to examine the influence of vascular endothelial growth factor (VEGF) inhibition on endothelial cell fenestration. Animal study. Four Cynomolgus monkeys received an intravitreal injection of 1.25 mg bevacizumab. The eyes were enucleated and prepared for light and electron microscopy on days one, four, seven, and 14. Control eyes remained untreated. Choriocapillaris endothelial cell fenestrations were quantified. Choriocapillaris endothelial cell fenestrations were significantly reduced after intravitreal injection of bevacizumab. Fenestration was lowest on day four (15.9 +/- 6.7 per 25 microm) and increased again from days seven to 14, but was still significantly lower than in the control (66.2 +/- 9.5 per 25 microm). Densely packed thrombocytes and leukocytes regionally occluded the choriocapillaris lumen of treated eyes. On day one an increased number of leukocytes filled in the choriocapillaris lumen. Photoreceptors were damaged in two of 40 light microscopic sections. On days one to seven, choroidal melanocytes contained giant melanosomes. None of these described features was found in controls. Intravitreal bevacizumab causes ultrastructural changes in the choriocapillaris of primate eyes. A significant reduction of choriocapillaris endothelial cell fenestrations is seen as early as 24 hours after injection and their number increases again after two weeks. These findings may play a role in the early clinical effect of intravitreal bevacizumab for macular edema. Because an increased risk of circulation disturbances in the choriocapillaris cannot be excluded, patients should be carefully monitored.

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Author and article information

Journal

Journal ID (nlm-ta): Case Report Ophthalmol

Journal ID (publisher-id): COP

Title: Case Reports in Ophthalmology

Publisher: S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )

ISSN (Electronic): 1663-2699

Publication date Collection: Sep-Dec 2011

Publication date (Electronic): 23 September 2011

Publication date PMC-release: 23 September 2011

Volume: 2

Issue: 3

Pages: 314-318

Affiliations

[1] ^aDivision of Ophthalmology, Department of Organ Therapeutics, Kobe University Graduate School of Medicine, Kobe Kaisei Hospital, Kobe, Japan

[2] ^bDepartment of Ophthalmology, Kobe Kaisei Hospital, Kobe, Japan

Author notes

*Hisanori Imai, MD, PhD, Department of Ophthalmology, Kobe Kaisei Hospital, 3-11-15 Shinoharakitamati, Nada-ku, Kobe 657-0068 (Japan), Tel. +81 78 871 5201, E-Mail imai@ 123456kobe-kaisei.org

Article

Publisher ID: cop0002-0314

DOI: 10.1159/000332830

PMC ID: 3220908

PubMed ID: 22125532

SO-VID: 6dac1d2e-bcdb-4b7a-be10-54aff61d9890

License:

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