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C. D. Leahy, E. J. Ellis, J. Y. Ellis, K. S. Crawford; Efficacy of a Topical Ocular Drug Delivery Device (TODDD) for the Treatment of Glaucoma by Telemetric Measurement of IOP in the Normal Rabbit. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5816.
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To demonstrate the sustained 90-day delivery and efficacy of a topical ocular drug delivery device (TODDD), by delivering timolol in vivo, continuously monitoring IOP using telemetry, and comparing ocular and systemic levels to those of standard treatment with topical drops.
Telemetry manometer devices from DSI (St. Paul, MN) were surgically implanted into one eye of 4 rabbits. IOP data was collected continuously from unrestrained animals over a 14 week period. Data were averaged and results reported for each 30-minute time point. After stabilization of the normal diurnal pattern of IOP, a TODDD containing a low concentration of timolol by weight was placed on the conjunctiva of one eye followed by a partial tarsorrhaphy. The drug diffuses continuously out of the solid matrix device, leaving the delivery device matrix and overall shape intact. Daily observations and monthly full clinical examinations were performed to verify the placement of the device and assess ocular tolerance. IOP reduction was determined based on pre-timolol diurnal curves in the same eye. Aqueous and blood plasma samples were taken at baseline and at necropsy.
The TODDD was well tolerated, with minimal to no corneal or intraocular irritation. The IOP-lowering effect, seen as a decrease in the amplitude of the circadian fluctuation in the normal rabbit, was maintained for the entire three months of the study, with statistical significance at weeks 3-12. The maximal IOP reduction in these normotensive animals was 5.5 mmHg, representing a 37% reduction in IOP from the pre-timolol average. The IOP effect was slightly greater than that typically observed with topical timolol drop treatment in this species. Systemic levels of drug were <0.1 ng/mL (limit of detection) in the animals treated with the TODDD vs. 8.49 ng/mL in an animal treated with timolol drops for one week.
IOP results indicate that sustained release and efficacy was achieved after two weeks of treatment that continued for the entire three-month treatment period. The IOP-lowering effect was comparable to perfect compliance with drops. These results, along with the timolol blood level data, indicate that this device is able to deliver therapeutic levels of drug to the target area while minimizing systemic exposure.
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