| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Divison of Bioengineering and Physical Sciences, Office of Research Services; 3National Eye Institute; the 4MRI Research Facility, National Institute of Neurological Disease and Strokes; and the 5Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; and the 2Department of Chemical Engineering, University of Maryland, College Park, Maryland.
PURPOSE. The ability of an episcleral implant at the equator of the eye to deliver drugs to the posterior segment was evaluated, using a sustained-release implant containing gadolinium-DTPA (Gd-DTPA). The movement of this drug surrogate was assessed with magnetic resonance imaging (MRI) in the rabbit eye. The results were compared with a similar implant placed in the vitreous cavity through a scleral incision at the equator.
METHODS. Polymer-based implants releasing Gd-DTPA were manufactured and placed in the subconjunctival space on the episclera or in the vitreous cavity in live rabbit eyes (in vivo) and in freshly enucleated eyes (ex vivo). Release rates of implants in vitro were also determined. Dynamic three-dimensional MRI was performed using a 4.7-Tesla MRI system for 8 hours. MR images were developed and analyzed on computer.
RESULTS. Episcleral implants in vivo delivered a mean total of 2.7 µg Gd-DTPA into the vitreous, representing only 0.12% of the total amount of compound released from the implant in vitro. No Gd-DTPA was detected in the posterior segment of the eye. Ex vivo, the Gd-DTPA concentration in the vitreous was 30 times higher. In vivo eyes with intravitreal implants placed at the equator delivered Gd-DTPA throughout the vitreous cavity and posterior segment. Compartmental analysis of the ocular drug distribution from an episcleral implant showed that the elimination rate constant of Gd-DTPA from the subconjunctival space into the episcleral veins and conjunctival lymphatics was 3-log units higher than the transport rate constant for Gd-DTPA movement into the vitreous.
CONCLUSIONS. In vivo, episcleral implants at the equator of the eye did not deliver a significant amount of Gd-DTPA into the vitreous, and no compound was identified in the posterior segment. A 30-fold increase in vitreous Gd-DTPA concentration occurred in the enucleated eyes, suggesting that there are significant barriers to the movement of drugs from the episcleral space into the vitreous in vivo. Dynamic three-dimensional MRI using Gd-DTPA, and possibly other contrast agents, may be useful in understanding the spatial relationships of ocular drug distribution and clearance mechanisms in the eye.
This article has been cited by other articles:
|
|
 |
|
  S. J. Lee, E. S. Kim, D. H. Geroski, B. E. McCarey, and H. F. Edelhauser Pharmacokinetics of Intraocular Drug Delivery of Oregon Green 488-Labeled Triamcinolone by Subtenon Injection Using Ocular Fluorophotometry in Rabbit Eyes Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4506 - 4514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Amrite, H. F. Edelhauser, and U. B. Kompella Modeling of Corneal and Retinal Pharmacokinetics after Periocular Drug Administration Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 320 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Lee, H. Kim, N. S. Wang, P. M. Bungay, B. C. Gilger, P. Yuan, J. Kim, K. G. Csaky, and M. R. Robinson A Pharmacokinetic and Safety Evaluation of an Episcleral Cyclosporine Implant for Potential Use in High-Risk Keratoplasty Rejection Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2023 - 2029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ghate, W. Brooks, B. E. McCarey, and H. F. Edelhauser Pharmacokinetics of Intraocular Drug Delivery by Periocular Injections Using Ocular Fluorophotometry Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2230 - 2237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Lindsey, J. G. Crowston, A. Tran, C. Morris, and R. N. Weinreb Direct Matrix Metalloproteinase Enhancement of Transscleral Permeability Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 752 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Kim, C. J. Galban, R. J. Lutz, R. L. Dedrick, K. G. Csaky, M. J. Lizak, N. S. Wang, G. Tansey, and M. R. Robinson Assessment of Subconjunctival and Intrascleral Drug Delivery to the Posterior Segment Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 808 - 814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Pontes de Carvalho, M. L. Krausse, A. L. Murphree, E. E. Schmitt, P. A. Campochiaro, and I. H. Maumenee Delivery from episcleral exoplants. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4532 - 4539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. J. Cruysberg, R. M. M. A. Nuijts, D. H. Geroski, J. A. Gilbert, F. Hendrikse, and H. F. Edelhauser The Influence of Intraocular Pressure on the Transscleral Diffusion of High-Molecular-Weight Compounds Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3790 - 3794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kim, K. G. Csaky, B. C. Gilger, J. P. Dunn, S. S. Lee, M. Tremblay, F. de Monasterio, G. Tansey, P. Yuan, P. M. Bungay, et al. Preclinical Evaluation of a Novel Episcleral Cyclosporine Implant for Ocular Graft-Versus-Host Disease Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 655 - 662. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
