Transscleral diffusion delivery of chemotherapy is a promising way to reach the vitreal seeds of retinoblastoma, the most common intraocular malignancy in childhood. In this in vivo study, the delivery of topotecan via lens-shaped, bi-layered hydrogel implants was combined with transconjunctival cryotherapy to assess whether cryotherapy leads to higher concentrations of topotecan in the vitreous. The study included 18 New Zealand albino rabbits; nine rabbits received a topotecan-loaded implant episclerally and another nine rabbits received transconjunctival cryotherapy superotemporally 2 weeks before implant administration. Median vitreous total topotecan exposures (area under the curve, AUC) were 455 ng·h/mL for the cryotherapy group and 281 ng·h/mL for the non-cryotherapy group, and were significantly higher in the cryotherapy group, similar to maximum levels. Median plasma AUC were 50 ng·h/mL and 34 ng·h/mL for the cryotherapy and non-cryotherapy groups, respectively, with no statistically significant differences between them. In both groups, AUC values in the vitreous were significantly higher than in plasma, with plasma exposure at only approximately 11-12% of the level of vitreous exposure. The results confirmed the important role of the choroidal vessels in the pharmacokinetics of topotecan during transscleral administration and showed a positive effect of cryotherapy on intravitreal penetration, resulting in a significantly higher total exposure in the vitreous.

Clinical and Transplant Pathology Centre Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Department of Histology and Embryology 2nd Faculty of Medicine Charles University 150 06 Prague Czech Republic

Department of Medical Chemistry and Clinical Biochemistry 2nd Faculty of Medicine Charles University and Motol University Hospital 150 06 Prague Czech Republic

Department of Ophthalmology 2nd Faculty of Medicine Charles University and Motol University Hospital 150 06 Prague Czech Republic

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and Motol University Hospital 150 06 Prague Czech Republic

Department of Pharmacology 1st Faculty of Medicine Charles University and General University Hospital Prague 128 00 Prague Czech Republic

Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic 162 06 Prague Czech Republic

Moorfields Eye Hospital Abu Dhabi P O Box 62807 United Arab Emirates

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