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Jayakrishna Ambati, Evangelos S. Gragoudas, Joan W. Miller, Timothy T. You, Kazuaki Miyamoto, François C. Delori, Anthony P. Adamis; Transscleral Delivery of Bioactive Protein to the Choroid and Retina. Invest. Ophthalmol. Vis. Sci. 2000;41(5):1186-1191.
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purpose. To investigate the feasibility of transscleral drug delivery to the
choroid and retina.
methods. An osmotic pump was used to deliver IgG across the sclera of pigmented
rabbits, and levels were measured in the choroid, retina, vitreous
humor, aqueous humor, orbit, and plasma over 28 days. This method was
then used to deliver an anti–intercellular adhesion molecule-1
(ICAM-1) monoclonal antibody (mAb), and its effect on inhibiting
vascular endothelial growth factor (VEGF)–induced leukostasis in the
choroid and retina was determined by measuring tissue myeloperoxidase
results. Levels of retinal and choroidal IgG were significantly higher than
baseline at all points up to 28 days (P ≤ 0.01). IgG
levels in the orbit, vitreous humor, aqueous humor, and plasma were
negligible (P > 0.05). MPO activity in the choroid
of eyes treated with anti–ICAM-1 mAb was 80% less
(P = 0.01) than in eyes receiving an equal rate of
delivery of an isotype control antibody. Inhibition of MPO activity in
the retina was 70% (P = 0.01). The plasma
concentration of anti–ICAM-1 mAb was 31,000-fold less than the
concentration in the osmotic pump.
conclusions. Minimally invasive transscleral delivery can be used to deliver
therapeutic levels of bioactive drugs to the choroid and retina with
negligible systemic absorption. This method of ocular drug delivery may
be used in the treatment of a variety of chorioretinal
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