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T. M. Fife, R. A. P. Carvalho, G. G. Gum; Evaluation of the Effect on Intraocular Pressure of Transcleral Implants (TTDS Implants) Following Periocular Implantation in New Zealand White Rabbits. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5801.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of unidirectional episcleral drug delivery of various anti-glaucoma drugs on intraocular pressure (IOP).
24 New Zealand White rabbits (n = 4/group) were implanted with a targeted-transscleral drug delivery system (TTDS) in the right eye (OD) on day 0. Left eyes (OS) were used as control. The TTDS was implanted onto the bare scleral surface using transscleral buckling sutures. Implants contained a control pellet (positive control), a carbonic anhydrase inhibitor (acetazolamide), a beta-adrenergic antagonist (atenolol), a direct-acting miotic (pilocarpine), or a prostaglandin analog (latanoprost). Ethylene-vinyl-acetate (EVA) was used to formulate all the drugs, excluding latanoprost, where the commercially available ophthalmic formulation (Xalatan®) was injected directly into the implants. An additional control group received an empty implant that was evacuated on day 8 using a tuberculin syringe to create a negative-pressure environment inside the implant. IOP was measured three times a day utilizing a pneumatonometer. The area under the concentration-time curve (AUC) was calculated for the period from day 2 to day 5 (AUC2-5) and for day 2 to last day in the study (AUC2-last) and compared between OD and OS. A t-test (alpha = 0.05) was utilized to compare the AUC (mmHg*days) and daily mean IOP (mmHg) between test and control eyes.
The IOP increased transiently in OD and returned to normal levels within six hours following implantation. In all groups, the AUC2-5 was significantly lower OD compared to OS. The AUC2-last was significantly lower OD compared to OS in the groups where the device carried acetazolamide, pilocarpine and in those with empty implants. The average maximum decrease in IOP across all groups ranged from 4 to 5.5 mmHg between days 2 and day 5. The IOP returned to baseline levels day after day 2 or 3 for the control groups; pilocarpine and latanoprost groups showed significant differences between OD and OS up to day 5, atenolol up to day 8, and acetazolamide had the longest duration of effect with significant differences seen up to day 32 (last).
In this pilot study, we have demonstrated that selective transscleral delivery of anti-glaucoma drugs assisted by this TTDS is effective in decreasing the IOP. This can represent a viable alternative for prolonged therapeutics of glaucoma. Further studies are needed to characterize the additional benefits of utilizing sustained release formulations carrying more potent anti-hypertensive drugs.
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