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Surgery
Penetration of Bevacizumab into the Iris, Anterior Chamber Angle and
Ciliary Body After Intravitreal Injection
Swaantje Peters,
1,2
Peter Heiduschka,
1
Karl-Ulrich Bartz-Schmidt
1
and Ulrich Schraermeyer
1
1. University Eye Hospital, Tübingen; 2. University Eye Hospital, Lübeck
Abstract
Recently, it was suggested that the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab could be used in the treatment
of rubeosis iridis. Therefore, we aimed to trace the penetration of bevacizumab into the anterior chamber after intravitreal injection of the
drug. We found that intravitreally injected bevacizumab penetrates well and quickly into the anterior chamber angle, iris and ciliary body.
The highest concentration of bevacizumab is present on days one to four after injection, with penetration into the iris appearing to be faster
than that into the anterior chamber angle and ciliary body. These findings are consistent with the clinically described regression of iris
neovascularisation one to three days after injection. Furthermore, we demonstrated progressive penetration through the tissues of the
anterior chamber towards the sclera. Our study showed that the intravitreal application mode is suitable for obtaining an accumulation of
bevacizumab throughout the vascularised tissues of the anterior segment. Intravitreal bevacizumab may be used as a supplementary
treatment for rubeosis iridis and neovascular glaucoma.
Keywords
Bevacizumab, iris neovascularisation, rubeosis, ciliary body, anterior chamber angle, vascular endothelial growth factor (VEGF), immuno-
histochemistry, intravitreal injection
Disclosure: The authors have no conflicts of interest to declare.
Received: 19 April 2009 Accepted: 4 May 2009
Correspondence: Swaantje Peters, University Eye Hospital Lübeck, Ratzeburger Allee 160, D-23564 Lübeck, Germany. E:
Swaantje.Peters@googlemail.com
Rubeosis iridis, the formation of pathological vessels in the iris, is a Bevacizumab is a genetically engineered, humanised, monoclonal
severe complication of ischaemic retinal diseases such as proliferative antibody (MAb A.4.6.1) against all isoforms of VEGF-A and was
diabetic retinopathy or retinal vascular occlusion. The angiogenic approved by the US Food and Drug Administration (FDA) for the
cascade starts with a focal or generalised retinal hypoxia, which may adjuvant treatment of metastatic colorectal cancer in 2004. Since
appear in diabetic patients due to occlusive changes in the vessel wall 2005, there have been reports of the ‘off-label’ use of bevacizumab
and perfusion disturbances, as well as in all kinds of retinal vascular for ocular neovascular disease.
2–4
It was found that intravitreal
occlusive disease (branch or central retinal vein or artery occlusion). injection of bevacizumab is effective in reducing macular oedema and
lesion size of choroidal neovascular membranes, leading to a
A variety of pro-angiogenic growth factors are involved in the process of significant increase or stabilisation of visual acuity.
5
It was shown that
angiogenesis, although vascular endothelial growth factor A (VEGF-A) VEGF-induced permeability and proliferation of choroidal endothelial
seems to be the most potent. For example, VEGF is twice as potent as cells can be completely inhibited by bevacizumab.
6
The number of
angiopoietin-2 in interrupting tight junctions in retinal endothelial cell endothelial cell fenestrations in the choriocapillaris is significantly
monolayers.
1
Retinal hypoxia upregulates VEGF-A expression, leading to reduced after intravitreal injection of bevacizumab.
7
the formation of leaky retinal neovascularisation. The high
concentrations of VEGF-A also reach the vitreous and the anterior Although retinal and choroidal neovascularisation are the main
chamber, and in this way act on the tissues of the anterior segment, scope of application for bevacizumab, clinical case reports
leading to the formation of neovascularisation in the chamber angle and described a quick regression of leaky iris neovascularisation after
the iris. These neovascularisations can reduce visual acuity due to intravitreal injection of bevacizumab.
8
At this time, no experimental
haemorrhages, and they also impair the drainage of aqueous humour in work had been published on the effects or time-related distribution
the chamber angle, leading to secondary neovascular glaucoma, which of bevacizumab on the vascularised tissues of the anterior
is a severe complication of retinal ischaemic disease. This leads to segment; neither was it known whether the intravitreal or
damage of the optic nerve. intracameral application mode was superior.
The existing treatment options – such as pan-retinal photocoagulation, In terms of the posterior segment, there was intense discussion
cryotherapy or cyclodestructive procedures – often do not generate about whether bevacizumab has the ability to penetrate the retina
satisfying results. Recently, use of anti-VEGF antibody bevacizumab in in order to effect pathological choroidal neovascularisation. The
the treatment of rubeosis iridis was suggested. reason for this debate was a study from Mordenti et al.
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