Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014, 158(4):552-556 | DOI: 10.5507/bp.2012.106

Retinal toxicity after repeated intravitreal carboplatin injection into rabbit eyes

Pavel Pochopa, Denisa Darsovaa, Jiri Uhlikb, Jan Lestakf, Jiri Kukackac, Daniela Kodetovad, Eva Klapkovac, Josef Malise, Ludek Vajnerb
a Department of Ophthalmology for Children and Adults, 2nd Faculty of Medicine, Charles University in Prague, Czech Republic
b Department of Histology and Embryology, 2nd Faculty of Medicine, Charles University in Prague
c Department of Clinical Biochemistry and Pathobiochemistry, 2nd Faculty of Medicine, Charles University in Prague
d Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague
e Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague
f Department of Ophthalmology, Clinic of Jan Lestak, Prague

Background: The aim of this study was to assess retinal toxicity in a rabbit model after carboplatin delivered as repeated transcorneal intravitreal injection, in order to determine the highest possible safe dose for use in human retinoblastoma "seeding" tumor chemotherapy.

Methods and Results: We used six albino rabbits in an in vivo experiment and injected 0.008 mg of carboplatin intravitreally (iv) 4 times at two-week intervals. 0.08 mL saline was injected into the left eye. We recorded electroretinograms (ERGs) before the first carboplatin injection and after the fourth injection. Platinum concentration was measured 1 h after the fifth additional injection. We found reduced dark-adapted b-wave amplitudes and, light-adapted b-wave and a-wave amplitudes. The differences between right and left eyes was significant but we found no histopathologic retinal changes.

Conclusions: 0.008 mg of carboplatin is probably the highest possible safe dose for the treatment of retinoblastoma patients. Questionable is direct extrapolation of retinal toxicity from the rabbit eye model to the human eye.

Keywords: carboplatin concentration, electroretinogram, intravitreal seeding, local treatment, rabbit, retinoblastoma

Received: July 13, 2012; Accepted: November 29, 2012; Prepublished online: December 10, 2012; Published: December 9, 2014  Show citation

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Pochop, P., Darsova, D., Uhlik, J., Lestak, J., Kukacka, J., Kodetova, D., ... Vajner, L. (2014). Retinal toxicity after repeated intravitreal carboplatin injection into rabbit eyes. Biomedical papers, 158(4), 552-556. doi: 10.5507/bp.2012.106
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    References

    1. Hayden BC, Jockovich ME, Murray TG, Voigt M, Milne P, Kralinger M, Feuer WJ, Hernandez E, Parel JM. Pharmacokinetics of systemic versus focal carboplatin chemotherapy in rabbit eyes: possible implication in the treatment of retinoblastoma. Invest Ophthalmol Vis Sci 2004;45:3644-9. Go to original source... Go to PubMed...
    2. Mendelsohn ME, Abramson DH, Madlen T, Tong W, Tran HT, Dukel IJ. Intraocular concentrations of chemotherapeutic agents after systemic or local administration. Arch Ophthalmol 1998;116:1209-12. Go to original source... Go to PubMed...
    3. Wilson TW, Chan HSL, Moselhy GM, Heydt DD Jr, Frey CM, Gallie BL. Penetration of chemotherapy into vitreous is increased by cryotherapy and cyclosporine in rabbits. Arch Ophthalmol 1996;114:1390-5. Go to original source... Go to PubMed...
    4. Kaneko A, Suzuki S. Eye-Preservation Treatment of Retinoblastoma with Vitreous Seeding. Jpn J Clin Oncol 2003;33:601-7. Go to original source... Go to PubMed...
    5. Velez G, Yuan P, Sung C, Tansey G, Reed GF, Chan CC, Nussenblatt RB, Robinson MR. Pharmacokinetics and Toxicity of Intravitreal Chemotherapy for Primary Intraocular Lymphoma. Arch Ophthalmol 2001;119:1518-24. Go to original source... Go to PubMed...
    6. Shield JA, Shields CL. Intraocular Tumors: A Text and Atlas. Philadelphia, Pa: WB Saunders Co. 1992:305-91.
    7. Pochop P, Darsova D, Kukacka J, Tesfaye H, Vajner L, Uhlik J, Kodetova D, Malis J, Dotrelova D. Intravitreal carboplatin concentration and area under concentration versus time curve after intravitreal and periocular delivery. Eur J Ophthalmol 2010; 20:745-51. Go to original source... Go to PubMed...
    8. Cohen VM, Shields CL, Fruta M, Shields JA. Vitreous Seeding From Retinal Astrocytoma in Three Cases. Retina 2008;28:884-8. Go to original source... Go to PubMed...
    9. Karcioglu ZA. Fine Needle Aspiration Biopsy (FNAB) for Retinoblastoma. Retina 2002;22:707-10. Go to original source... Go to PubMed...
    10. Harbour JW, Murray TG, Hamasaki D, Cicciarelli N, Hernández E, Smith B, Windle J, O'Brien JM. Local carboplatin therapy in transgenic murine retinoblastoma. Invest Ophthalmol Vis Sci 1996; 37:1892-8. Go to original source...
    11. Pochop P, Darsova D, Uhlik J, Lestak J, Kukacka J, Kodetova D, Vajner J, Malis J, Dotrelova D. Evaluation of retinal toxicity of carboplatin after repeated transcorneal intravitreal injection. In: Monduzzi editor. Proceedings of the 8th International Symposium on Ocular Pharmacology and Therapeutics - ISOPT, Rome, Italy, 2009 3-6 December; Bologna; 2009. p. 155-161.
    12. Pradue MT, Hejny C, Gilbert JA, Phillips MJ, Geroski DH, Edelhauser HF. Retinal function after subconjunctival injection of carboplatin in fibrin sealant. Retina 2004; 24:776-82. Go to original source... Go to PubMed...
    13. Rothenberg SJ, Schnaas L, Salgado-Valladares M, Casanueva E, Geller AM, Hudnell HK, Fox DA. Increased ERG a- and b-Wave Amplitudes in 7- to 10-Year-Old Children Resulting from Prenatal Lead Exposure. Invest. Ophthalmol Vis Sci 2002;43:2036-44. Go to PubMed...
    14. Kremmer S, Tolksdof-Kremmer A, Stodtmeister R. Simultaneous registration of VECP and pattern ERG during artificially raised intraocular pressure. Ophthalmologica 1995;209:233-41. Go to original source... Go to PubMed...
    15. Zhao H, Ai Y, Niu C, Guan W, Li X, Qin L. Research on Influences of Transient High IOP during LASIK on Retinal Functions and Ultrastructure. J Ophthalmol. 2009;2009:230528. Go to original source... Go to PubMed...
    16. Polito A, Cereda M, Romanelli F, Pertile G. Macular translocation with 360 degrees retinotomy for management of retinal pigment epithelial tear: long-term results. Br J Ophthalmol 2010;95:74-8. Go to original source... Go to PubMed...

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