Peters_subbed_final_Layout 1 01/09/2009 12:23 Page 38
Surgery
(see Figure 2) and the ciliary body (see Figure 3). In all of these Certain blood vessels showed strong immunoreactivity for
tissues of the anterior segment, bevacizumab is preferably located bevacizumab in their lumen (see Figures 2 and 3). Assuming a
in the vessel walls, which are the sites of secretion and binding of regular circulation, a rapid distribution and subsequent elimination
VEGF to its receptors on the vascular endothelial cells.
12
The same of intravascular bevacizumab would be expected. The selective
accumulation of the antibody in certain vessels may be a sign of
disturbed circulation in some of the blood vessels, as previously
observed in the choriocapillaris.
7
If the intraocular pressure is high, the use
We demonstrated that the intravitreal application mode is suitable
of a local antiglaucomatous treatment or
to obtain an accumulation of bevacizumab throughout the
cyclodestructive and filtering surgery
vascularised tissues of the anterior segment. The highest
concentration of bevacizumab is seen between days one and four,
becomes necessary.
and it regresses by day 14. The vessel walls are the target sites
for VEGF and therefore show an accumulation of the VEGF
antibody bevacizumab in the anterior segment, as well as in
the choriocapillaris. Given the persistent intraluminal location
distribution is true for the choriocapillaris (see Figure 4). The of bevacizumab in certain vessels, perfusion disturbances cannot
highest concentration of bevacizumab is present on days one to be excluded.
four after injection, the penetration into the iris appearing to be
faster (day one) than that into the anterior chamber angle and Clinically, bevacizumab may be used as a supplementary treatment
ciliary body (day four). for rubeosis iridis and neovascular glaucoma. Although it is not a
causative treatment, it has several advantages for the patient. First,
These findings are consistent with the clinically described the risk of haemorrhages and subsequent deterioration of visual
regression of iris neovascularisation one to three days after acuity may be reduced. Second, if bevacizumab is used at an early
injection, and are also consistent with the observation that the stage of rubeosis, the formation of dense fibrovascular membranes
intracameral peak concentration of bevacizumab appears on day in the chamber angle and resulting neovascular glaucoma may be
three after intravitreal injection.
13
The intravitreal peak prevented. If applied at a later stage of the disease, progression
concentration and the anti-oedematous effect on the may still be inhibited. Nevertheless, additional procedures (pan-
choriocapillaris were found to be present on day four,
7
obviously retinal photocoagulation, cryotherapy) to lower VEGF secretion in
paralleling the situation in the anterior chamber. Bevacizumab the hypoxic retina are required. If the intraocular pressure is high,
immunoreactivity in the iris on day one (see Figure 2) is more the use of a local antiglaucomatous treatment or cyclodestructive
intense and abundant than in the anterior chamber angle or in the and filtering surgery becomes necessary. n
ciliary body, but it then appears to be eliminated more quickly than
from the ciliary body. The latter shows an intense positivity for
Swaantje Peters is a Consultant at the University Eye
bevacizumab even on day 14 (see Figure 3).
Hospital Lübeck in Germany. She specialises in
electron microscopy and various aspects of cell
In the chamber angle, there was a time-related distribution of
culture, particularly endothelial cells, and has received
grants and fellowships from the Association for
bevacizumab: on day one after injection more intense staining was
Research in Vision and Ophthalmology (ARVO), the
present on the side of Schlemm’s canal facing the anterior chamber German Ophthalmology Association (DOG) and
(see
Diabetes UK. Dr Peters attended medical school in
Figure 1), while on day four the staining was more intense on
Bonn, Montpellier, Perth and Cologne. During her
the exterior side facing the sclera. This finding may reflect a
residency in Cologne, Portsmouth, London (Moorfields Institute of Ophthalmology)
progressive penetration through the tissue from the anterior and Tübingen, she performed laboratory investigations in the field of ocular
chamber towards the sclera, paralleling the progressive penetration
angiogenesis and pigmentation and was involved in clinical trials on ocular
neovascular disease.
of bevacizumab through the retinal layers during the first week, as
described by Heiduschka et al.
10
1. Peters S, Cree IA, Alexander R, et al., Angiopoietin 2005;36(4):336–9. pharmacokinetics, and safety of 125I-labeled full-length
Modulation of Vascular Endothelial Growth Factor: 5. Rich RM, Rosenfeld PJ, Puliafito CA, et al., Short-term and Fab antibodies in rhesus monkeys following
Effects on Retinal Endothelial Cell Permeability, Cytokine, safety and efficacy of intravitreal bevacizumab (Avastin) intravitreal administration, Toxicol Pathol, 1999;27:536–44.
2007;40(2):144–50. for neovascular age-related macular degeneration, 10. Heiduschka P, Fietz H, Hofmeister S, et al., Penetration of
2. Michels S, Rosenfeld PJ, Puliafito CA, et al., Systemic Retina, 2006;26:495–511. bevacizumab through the retina after intravitreal injection
bevacizumab (Avastin) therapy for neovascular age- 6. Peters S, Julien S, Heiduschka P, et al., Anti-permeability in monkey, Invest Ophthalmol Vis Sci, 2007;48(6):2814–23.
related macular degeneration twelve-week results of an and anti-proliferative effects of standard and frozen 11. Peters S, Heiduschka P, Julien S, et al.,
uncontrolled open-label clinical study, Ophthalmology, bevacizumab on choroidal endothelial cells, Br J Immunohistochemical localization of intravitreally
2005;112(6):1035–47. Ophthalmol, 2007;91(6):827–31. injected bevacizumab in the anterior chamber angle, iris
3. Reichel E, Intravitreal bevacizumab for choroidal 7. Peters S, Heiduschka P, Julien S, et al., Ultrastructural and ciliary body of the primate eye, Br J Ophthalmol,
neovascularization and cystoid macular edema: a cost- findings in the primate eye after intravitreal injection of 2008;92(4): 541–4.
effective treatment?, Ophthalmic Surg Lasers Imaging, bevacizumab, Am J Ophthalmol, 2007;143(6):995–1002. 12. Simorre-Pinatel V, Guerrin M, Chollet P, et al., Vasculotropin-
2005;36(4):270–71. 8. Grisanti S, Biester S, Peters S, et al., Intracameral VEGF stimulates retinal capillary endothelial cells through an
4. Rosenfeld PJ, Fung AE, Puliafito CA, Optical coherence bevacizumab for iris rubeosis, Am J Ophthalmol, autocrine pathway, Invest Ophthalmol Vis Sci, 1994;35:3393–3400.
tomography findings after an intravitreal injection of 2006;142:158–60. 13. Bakri SJ, Snyder MR, Reid JM, et al., Pharmacokinetics of
bevacizumab (Avastin) for macular edema from central 9. Mordenti J, Cuthbertson RA, Ferrara N, et al., intravitreal bevacizumab (Avastin), Ophthalmology,
retinal vein occlusion, Ophthalmic Surg Lasers Imaging, Comparisons of the intraocular tissue distribution, 2007;114: 855–9.
38 EUROPEAN OPHTHALMIC REVIEW
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