Abstract
Purpose :
Intracameral implants providing sustained release of drug to lower intraocular pressure (IOP) have the potential to bypass the ocular surface and manage IOP in glaucoma without use of daily eye drops. To facilitate the development of intracameral drug implants for lowering IOP, we developed a dog model to determine optimal drug release rates in the intracameral space.
Methods :
Female normotensive Beagle dogs were used (n=5-8 per treatment). Under general anesthesia, an Alzet osmotic microinfusion pump was surgically placed subcutaneously in the back of the neck of each dog, with a cannula opening into the intracameral space of the right eye; the main body of the cannula was sutured to the sclera. Patency of the cannula was confirmed with fluorescein (Figure). After recovery from surgery, a solution of prostaglandin/prostamide analog at varying concentrations was delivered continuously into the intracameral space at 2.5 μL/hr for 10 to 15 days. Aqueous humor samples were collected to determine drug concentration. IOP was measured in awake animals with a TonoVet rebound tonometer.
Results :
Infusion of bimatoprost, bimatoprost acid, or latanoprost acid lowered IOP; infusion of latanoprost did not affect IOP. The IOP lowering during bimatoprost infusion was relatively steady and sustained. When the infused bimatoprost dose was increased to two higher doses, the magnitude of IOP lowering was similar, ranging from -32.9% to -34.3% at steady state with no clear dose-dependency. The aqueous humor bimatoprost concentration increased with increasing bimatoprost dose; bimatoprost acid was detected only at the highest dose. These results suggest that the lowest dose would represent a good target release rate when developing an intracameral bimatoprost drug implant. Ophthalmic observations were as expected with the surgical procedure, and no adverse findings were attributed to the tested drugs.
Conclusions :
This dog model can be used to effectively screen IOP-lowering drugs as candidates for intracameral sustained-release platforms. Use of this model system to determine an optimal release rate and initial target dose to be used for in vivo testing of a sustained-release drug delivery device can accelerate intracameral implant drug development.
This is a 2021 ARVO Annual Meeting abstract.