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D. Whitmer, J. Lund, H. Hacker, J. Brown, M. Pitman, F. Palmer, K. Jenkins, B. Stuck; Topical Drug Therapies for Laser Induced Retinal Injury. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4666. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Establish a technique for topical ophthalmic drug delivery in NHPs (Macaca fascicularis) using surgically implanted canulas and osmotic pumps. Using this method, evaluate the initial morphologic cellular responses of Argon laser induced retinal injury to neuroprotective and anti-inflammatory effects of α-2 agonist, non-steroidal and steroid drugs applied topically and via intravitreal injection in the Cynomologous monkey (Macaca fascicularis).
Twenty two sterile vinyl canulas and osmotic pumps (Alzet) were surgically implanted in 11 male anesthetized Cynomologous monkeys (n=22). Canulas were placed bilaterally in the lateral canthus conjunctiva, buried subcutaneously to the inter-scapular region then connected to an osmotic pump buried subcutaneously. Twelve Argon laser (514 nm, 50 mW, 100 ms) lesions were created in the parafoveal macula in two parallel rows (superior and inferior to the fovea) in both eyes of four canulated monkeys (n=96). Topical application to the cornea and sclera of each drug (brimonidine and ketorolac) in both eyes of each monkey was administered at 5.0 µl/hr/24 hrs for 30 days. An intravitreal injection of sterile triamcinolone acetonide (0.5 mg) was performed on one eye of each monkey. Initial (days 1, 3, 14 and 28) retinal morphological responses to injury and treatment were evaluated using color fundus photos, fluorescein angiography and OCT/SLO imaging.
93% of 22 canulas implanted were retained and functional at day 21 post surgery and 86% at day 45. The most common post operative complications were cellulitis (5%)at one of more incisions and corneal ulceration (9%) due to canula displacement. Area measurements of OCT images of RPE and photoreceptor laser induced injury showed brimonidine solely and brimonidine plus steroid injection produced the largest reduction of injury area in 30 days (65.5% treated vs 14% non- treated control).
This drug delivery method allows extended topical ophthalmic drug delivery in NHPs to investigate ocular pharmacological effects without multiple daily sedations or excessive handler risk. Topical application of ophthalmic medication is a viable drug delivery approach for investigating effective treatments of laser induced retinal injury.
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