Mj. Tolentino et al., Angiography of fluoresceinated anti-vascular endothelial growth factor antibody and dextrans in experimental choroidal neovascularization, ARCH OPHTH, 118(1), 2000, pp. 78-84
Objective: To determine if anti-vascular endothelial growth factor antibody
and a range of dextrans with varying diffusion radii and molecular weights
are permeable through experimental choroidal neovascularization (CNV).
Methods: Choroidal neovascularization was induced in 10 cynomolgus monkey r
etinas by means of argon laser injury. Digital fundus fluorescein angiogram
s were performed with fluorescein sodium: fluoresceinated IgG antibodies (a
nti-vascular endothelial growth factor and a control antibody), and fluores
ceinated dextrans with molecular weights of 4, 20, 40, 70 and 150 kd. The 4
0- and 70-kd dextrans straddle the effective diffusion radius of IgG. For e
ach reagent, early and late angiograms were performed in a standardized fas
hion, with follow-up images obtained to monitor residual fluorescence.
Results: Perfusion of retinal vessels and choroidal vasculature was seen wi
th all reagents. Fluorescein and 4-and 20-kd dextran leaked rapidly from th
e CNV within the first minute. Angiography with the use of 40-kd dextran an
d fluoresceinated antibody, either anti-vascular endothelial growth factor
or control IgG, showed fluorescence within the CNV that increased during th
e first 1 to 5 hours, with mild leakage from the CNV. By 24 hours, fluoresc
ence in the CNV was minimal, although in some cases persistent fluorescence
in the surrounding tissue was evident up to 2 weeks. The 70-kd dextran sho
wed fluorescence within the CNV and leakage in 1 of 3 eyes, The 150-kd dext
ran showed fluorescence within the CNV but did not demonstrate leakage.
Conclusions: Fluoresceinated antibodies and dextran with smaller effective
diffusion radii showed CNV perfusion and leakage. Dextrans with larger effe
ctive diffusion radii (70 kd and 150 kd) perfused into CNV but did not show
leakage consistently.
Clinical Relevance: Determining the permeablity of antibodies and molecules
of similar size through CNV can help ascertain the feasibility of using in
travenously administered antibodies against angiogenic growth factors as a
future treatment for choroidal neovascularization.