May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
In vivo MRI of Transscleral Drug Delivery Into the Anterior Segment
Author Affiliations & Notes
  • S. S. Lee
    Biomedical Engineering, University of Southern California, Los Angeles, California
    Childrens Hospital Los Angeles, Los Angeles, California
  • P. Sharma
    Biomedical Engineering, University of Southern California, Los Angeles, California
  • D. Z. D'Argenio
    Biomedical Engineering, University of Southern California, Los Angeles, California
  • R. A. Moats
    Childrens Hospital Los Angeles, Los Angeles, California
  • Footnotes
    Commercial Relationships  S.S. Lee, None; P. Sharma, None; D.Z. D'Argenio, None; R.A. Moats, None.
  • Footnotes
    Support  Allergan Unrestricted Educational Grant
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3193. doi:
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      S. S. Lee, P. Sharma, D. Z. D'Argenio, R. A. Moats; In vivo MRI of Transscleral Drug Delivery Into the Anterior Segment. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3193.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Subconjunctival injections of some compounds are more effective in delivering drug to the anterior segment than to the vitreous cavity. In-vivo imaging studies in rabbits with magnetic resonance imaging (MRI) have identified a facilitated area of entry of a drug surrogate from the episcleral space that transits through the pars plicata to the aqueous humor in vivo. Exploiting this anterior portal of entry may be advantageous for sustained delivery of aqueous humor production suppressants for treating ocular hypertension and glaucoma. To improve our understanding of drug movement through the anterior portal, we performed in-vivo imaging with a high-resolution MRI (7 Tesla) following anterior sub-Tenon’s injection of a drug surrogate.

Methods: : Anterior sub-Tenon’s injections (10 ul volume) in the superotemporal quadrant were performed in rats (Sprague Dawley) with Gd-DTPA that acted as drug surrogate. Rats received either 0.05M of Gd-DTPA (Magnevist, Berlex , Inc.) in PBS, or 0.05M of Gd-DTPA (Magnevist, Berlex, Inc.) in 4% hydroxypropyl methyl cellulose (HPMC). Injections were performed with a Hamilton syringe with an attached 30 G hypodermic needle oriented parallel and 1 mm posterior to the limbus. Serial 3-D MRI scans (7.0 T Pharmascan, Bruker) were performed until the formulation was undetectable. Tissues of interest were manually segmented (Image J) and drug concentrations were estimated using a calibration curve relating signal intensity to drug concentration.

Results: : PBS and HPMC drug depots were detectable in the sub-Tenon’s space for a mean time of 85.5 minutes and 156.5 minutes, respectively. The temporal ciliary body in the HPMC group, which was closest to the drug depot, exhibited drug concentrations were on average 83.2% greater than the nasal ciliary body of the same eye. The ciliary body concentrations in the PBS group were undetectable. Aqueous humor concentrations of the injected eyes increased over time in both formulation groups, while vitreous humor concentrations remained low.

Conclusions: : The pars plicata region appears to be a portal of drug entry into the eye following an anterior sub-Tenon’s injection. There is a steep concentration gradient from the sub-Tenon’s drug depot to the adjacent ciliary body region, and into the aqueous humor. This anterior portal region for facilitated drug transit can be exploited to treat anterior segment diseases.

Keywords: anterior segment • sclera • imaging/image analysis: non-clinical 
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