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Paula Schaiquevich, Paula Taich, Flavio Requejo, Marcelo Asprea, Mariana Sgroi, Pierre Gobin, David H Abramson, Guillermo Chantada; Ophthalmic artery chemosurgery as a local route for optic nerve delivery of chemotherapy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3685.
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© ARVO (1962-2015); The Authors (2016-present)
Extraocular retinoblastoma is a major challenge worldwide especially in developing countries. Current treatment includes systemic chemotherapy combined with radiation. However, there is a clear need of improvement of chemotherapy bioavailability in the optic nerve as a target site of tumor spread. Thus, the aim of the study was to evaluate the ophthalmic artery chemosurgery (OAC) local route for chemotherapy delivery assessing the ocular and optic nerve exposure to chemotherapy and to compare it to exposure after intravenous infusion (IV) of the same dose in an animal model.
Landrace pigs (n=5) received 4mg of topotecan infused through OAC as performed in retinoblastoma patients. At the end of the infusion, the eyes were enucleated, the optic nerve and retina were dissected, and the vitreous and plasma were separated. Then, the animals were recovered and after a wash-out period, the animals received a 30-min IV infusion of topotecan (4 mg). The remaining eye was enucleated and tissues and fluids were separated. All samples were stored until quantitation using HPLC.
A significantly higher concentration of topotecan in the optic nerve, vitreous, and retina was obtained in eyes after OAC compared to IV infusion (p<0.05). The median (range) ratio between topotecan concentration after OAC to IV infusion in the optic nerve, retina and vitreous was 84(54-668), 143(49-200) and 246(56-687), respectively. However, topotecan systemic exposure after OAC and IV infusion remained comparable (p>0.05). The median (range) optic nerve-to-plasma ratio after OAC and IV was 44(16-59) and 0.35 (0.03-0.95), respectively.
Topotecan OAC delivery attained an 80-fold higher concentrations in the optic nerve compared to the systemic infusion of the same dose with similar plasma concentration in a swine model. Patients with retinoblastoma extension into the optic nerve may benefit from OAC for tumor burden by increased chemotherapy bioavailability in the optic nerve without increasing systemic exposure or toxicity.
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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