Transscleral delivery of bioactive protein to the choroid and retina.
OBJECTIVE
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 (MPO) activity.


RESULTS
Levels of retinal and choroidal IgG were significantly higher than baseline at all points up to 28 days (P < or = 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 disorders.
Ambati
J
J
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA.
Gragoudas
E S
ES
Miller
J W
JW
You
T T
TT
Miyamoto
K
K
Delori
F C
FC
Adamis
A P
AP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001082:Aqueous Humor / Q000201:enzymology / Q000276:immunology; D002829:Choroid / Q000201:enzymology / Q000276:immunology*; D016503:Drug Delivery Systems; D016228:Endothelial Growth Factors / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000032:analysis; D015918:Infusion Pumps, Implantable; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000201:enzymology / Q000276:immunology*; D012590:Sclera / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014822:Vitreous Body / Q000201:enzymology / Q000276:immunology
D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D007074:Immunoglobulin G; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase