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Brian C. Tse, Jena J. Steinle, Barrett G. Haik, Matthew W. Wilson; Effects of Supra-Selective Intra-Ophthalmic Artery Chemotherapy (SSIOAC) on Orbital Arteries in a Non-Human Primate Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1878.
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Supra-selective intra-ophthalmic artery chemotherapy (SSIOAC) has come to the forefront in the management of retinoblastoma (RB) without benefit of preclinical data. Although observed clinical complications include ophthalmic artery (OA) thrombosis, full effects of SSIOAC on orbital vasculature are unknown. Here in, we report the histopathology of orbital arteries in a non-human primate (NHP) model of SSIOAC.
Six adult male Rhesus macaques (Macaca mulatta) underwent 3 cycles each of SSIOAC via the right OA at 3 week intervals. Three NHP were treated with melphalan (5mg/30ml), and 3 were treated with carboplatin (30mg/30ml) delivered over 30 minutes in a pulsatile fashion. The final SSIOAC was a terminal study, after which the eyes were enucleated and the animals perfused with formalin. The OA, its branches, and the optic nerves were dissected and submitted for standard histopathology processing. Arteries and optic nerves were serially sectioned and stained with hematoxylin and eosin.
Examination of right-sided vasculature revealed: OA and central retinal artery (CRA) dissection, OA intimal hyperplasia, disruption of the OA internal elastic lamina, CRA thrombosis, eyelid thrombosis, leukostasis of the pial vessels of the optic nerve, birefrigent crystals and foreign body giant cells, reactive membrane within the OA lumen. Findings were equally distributed among treatment cohorts. The left-sided vasculature and optic nerves were normal in all NHPs.
Observed structural changes such as dissection, intimal hyperplasia and fracturing of the internal elastic lamina in the treated orbital arteries favor mechanical trauma related to technique while the presence of thrombosis, leuokostasis, and birefrigent crystals suggest drug related toxicities. These potential complications should be taken into account before ultimately deciding upon SSIOAC for the treatment of retinoblastoma.
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