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Anthony B Daniels, Michael T. Froehler, Janene M. Pierce, Amy Nunnally, Thomas M. Bridges, Debra L. Friedman, Ann Richmond; A novel rabbit model of intraarterial chemotherapy / ophthalmic artery chemosurgery. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3667.
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© ARVO (1962-2015); The Authors (2016-present)
No small animal models of ophthalmic artery chemosurgery (OAC) exist. We have developed a rabbit model of OAC in order to be able to test the efficacy and toxicity of various drugs in a preclinical model system.
Femoral cut down was performed and the artery accessed and sheath placed. A microcatheter was advanced under fluoroscopic guidance and internal carotid artery (ICA) and external carotid artery (ECA) vasculature were interrogated angiographically to determine whether the ocular supply was via the internal or the external ophthalmic artery (OA). Ocular vascular supply was also confirmed by selective intraarterial fluorescein injection with retinal angiography as well as by selective vascular casting followed by ex vivo microCT. For chemotherapy treatments, the microcatheter was advanced up to the os of the dominant OA and 0.4 mg/kg melphalan was injected in a pulsatile fashion. For PK studies, following melphalan infusion, serial vitreous taps were obtained from both the treated and contralateral eye as well as from plasma up to 6 hours post treatment, and drug concentrations were measured by mass spectrometry. Eyes were subsequently harvested and in situ imaging mass spectrometry (IMS) was performed to measure intraretinal melphalan levels.
Angiography demonstrated several vascular variations, with ocular blood supply arising from either the internal OA off the ICA, from the external OA off the ECA, or from both, but was consistent between the two eyes of a given rabbit. This was confirmed by selective arterial fluorescein angiography as well as vascular casting followed by ex vivo microCT. Eye histopathology did not demonstrate retinal emboli or vascular damage. PK studies demonstrated a rapid rise in vitreous melphalan levels with a peak between 30-60 minutes post injection, followed by first order elimination with a half life of 1.6 hours. This was prolonged compared to the plasma half life of 1.1 hours, consistent with intraocular accumulation. In situ IMS demonstrated intraretinal as well as vitreous melphalan accumulation in the treated eyes.
OAC can be safely and reliably performed in a rabbit model system. There are several variations in rabbit ocular vascular supply, but ophthalmic arteries could be successfully accessed in all rabbits. PK studies and IMS demonstrate vitreous and retinal accumulation of melphalan in this model.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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