32.
Vitrectomy Development Anti-VEGF Antibody:
Preclinical, Clinical and Postclinical Studies
Ulrich Schraermeyer and the Tübingen Bevacizumab Study Group (Tübingen)
Purpose: Penetration of intravitreally injected bevacizumab (Avastin®) through the retina was
studied, due to speculation that a full-length antibody might not be able to penetrate the retina
as easily as an antibody fragment.
Methods: Six cynomolgus monkeys (Macaca fascicularis) were used. Two runs of intravitreal
injection into the right eyes, one with Avastin (group 1, four animals) and the other with Avastin
labelled with 125I (group 2, one animal). Group 1 animals were sacrificed 1, 4, 7 or 14 days
afterwards for subsequent histological analysis of the eyes by immuno-histochemistry, and the
group 2 animal was sacrificed 7 days afterwards for autoradiography and electron microscopy.
Funduscopy was performed before the injection and at several points afterwards. Blood samples
were collected at a different point from the group 2 animal. The sixth (control) animal remained untreated.
Results: No pathological changes were obvious in the funduscopic images. Bevacizumab immunoreactivity was found in the
choroid and inner layers of the retina one day after injection and spread to the outer layers and the choroid within the
following days, particularly to photoreceptors and blood vessels. Using Avastin® labelled with 125I, radioactivity could be
detected in blood serum one day after the intravitreal injection, and remained relatively stable until day 7.
Conclusions: The results show that the bevacizumab molecule can penetrate the retina and is also transported into the retinal
pigment epithelium, the choroid and particularly the photoreceptor outer segments after intravitreal injection of Avastin®.
Active transport mechanisms are involved.