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1From the Departments of Ophthalmology and 4Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland; 2The Children’s Hospital of Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California; and 33T Ophthalmics, Irvine, California.
PURPOSE. To assess the impact of an episcleral exoplant on transscleral delivery.
METHODS. New Zealand White rabbits were given a periocular injection of sodium fluorescein (fluorescein, 376 Da) or an episcleral exoplant loaded with fluorescein. Two types of exoplants were tested: (1) a rigid polyethylene device, impermeable on one side and open to the sclera on the other, that contained compressed pellets of fluorescein and was sutured loosely (apposition group) or tightly to indent the sclera (indentation group) and (2) flexible refillable silicone exoplants also open to the sclera that were secured by suturing, to form a sealed episcleral chamber that was filled with a fluorescein solution. Ocular and plasma fluorophotometry were performed at several time points, and histology was performed to evaluate the effect of exoplants on the periocular tissue.
RESULTS. Within 20 minutes of a periocular injection of fluorescein, peak fluorescence was visible in the anterior chamber (AC) and at later time points was displaced toward the retina; at all time points, the highest fluorescence was in the AC. For the polyethylene device indentation group, peak fluorescence was in the retina and posterior vitreous and spread to the AC over time. For the apposition exoplant group, two peaks of fluorescence were seen initially, one in the retina and posterior vitreous and one in the AC. The area under the concentration time curve (AUC ± SE) for fluorescein concentration was 144.4 ± 15.1 µg · h/mL for the retinal peak and 43.6 ± 7.1 µg · h/mL for the posterior vitreous peak after injection of 5 mg of fluorescein into a silicone exoplant, compared with a retinal peak of 3.9 ± 0.3 and a posterior vitreous peak of 0.99 ± 0.26 µg · h/mL after periocular injection of 5 mg of fluorescein (P < 0.01 for each). Peak plasma fluorescein levels were significantly reduced in the exoplant group compared with periocular injection.
CONCLUSIONS. An episcleral exoplant facilitates diffusion of fluorescein through the sclera resulting in high levels in the retina and posterior vitreous; levels are markedly increased compared with periocular injection of the same amount of fluorescein. It also reduces peak plasma levels indicating reduction of systemic absorption. This procedure provides a new approach that can be combined with sustained-release preparations to optimize delivery of agents to the retina and choroid while minimizing the potential for systemic toxicity.
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