Abstract
Purpose
To investigate the toxic effects of perfusion of intravitreal melphalan during vitrectomy on the rabbit retina.
Methods
We performed electoretinography (ERG) in 18 eyes of 18 healthy albino rabbits before and after intraocular melphalan perfusion at concentrations of 5-, 10-, and 20-μg/ml during pars plana vitrectomy. Fellow eyes that underwent vitrectomy without melphalan served as controls. The histopathologic retinal changes were observed in both eyes of two rabbits from each group.
Results
In the 5-μg/ml perfusion group, the ERGs and histology showed no substantial changes compared with control fellow eyes during 28 days postoperatively. In the 10- and 20-μg/ml groups, the mean a-wave amplitude decreased to 52% and 31% respectively of the fellow eye; the mean b-wave amplitude decreased to 52% and 19% respectively. However, the peak implicit time of the a- and b-waves did not significantly differ in the 10- and 20-μg/ml groups during 28 days postoperatively. Histologic sections showed necrosis of the inner nuclear layer and thinning of the outer nuclear layer in the 10-μg/ml group. Loss of the outer nuclear layer and the photoreceptor layer and necrosis of the inner nuclear layer were observed in the 20-μg/ml group.
Conclusion
The intravitreal 5-μg/ml melphalan perfusion during vitrectomy appears to be nontoxic to the retina. This therapeutic modality might be a potential treatment for retinoblastoma with vitreous seeding.
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References
Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68(4):820–823
Cassady JR, Sagerman RH, Tretter P, Ellsworth RM (1969) Radiation therapy in retinoblastoma. An analysis of 230 cases. Radiology 93(2):405–409
Sauerwein W, Hopping W, Bornfeld N (1997) Radiotherapy for retinoblastoma. Treatment strategies. Front Radiat Ther Oncol 30:93–96
Phillips C, Sexton M, Wheeler G, McKenzie J (2003) Retinoblastoma: review of 30 years’ experience with external beam radiotherapy. Australas Radiol 47(3):226–230
Scott IU, Murray TG, Feuer WJ, Van Quill K, Markoe AM, Ling S, Roth DB, O’Brien JM (1999) External beam radiotherapy in retinoblastoma: tumor control and comparison of 2 techniques. Arch Ophthalmol 117(6):766–770
Reese AB, Ellsworth RM (1964) Management of retinoblastoma. Ann N Y Acad Sci 114(2):958–962
Ellsworth RM (1969) The practical management of retinoblastoma. Trans Am Ophthalmol Soc 67:462–534
Gallie BL, Budning A, DeBoer G, Thiessen JJ, Koren G, Verjee Z, Ling, V, Chan HS (1996) Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophthalmol 114(11):1321–1328
Kingston JE, Hungerford JL, Madreperla SA, Plowman PN (1996) Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol 114(11):1339–1343
Murphree AL, Villablanca JG, Deegan WF 3rd, Sato JK, Malogolowkin M, Fisher A, Parker R, Reed E, Gomer CJ (1996) Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Arch Ophthalmol 114(11):1348–1356
Shields CL, De Pdotter P, Himelstein BP, Shields JA, Meadows AT, Maris JM (1996) Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol 114(11):1330–1338
Linn Murphree A (2005) Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin North Am 18(1):41–53, viii
Yamane T, Kaneko A, Mohri M (2004) The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma. Int J Clin Oncol 9(2):69–73
Kaneko A, Suzuki S (2003) Eye-preservation treatment of retinoblastoma with vitreous seeding. Jpn J Clin Oncol 33(12):601–607
Lagendijk JJ (1982) A microwave heating technique for the hyperthermic treatment of tumours in the eye, especially retinoblastoma. Phys Med Biol 27(11):1313–1324
Inomata M, Kaneko A (1987) Chemosensitivity profiles of primary and cultured human retinoblastoma cells in a human tumor clonogenic assay. Jpn J Cancer Res 78(8):858–868
Ueda M, Tanabe J, Suzuki T, Sakai H, Mochizuki K, Kitano K, Inomata M, Kaneko A (1994) Conservative therapy for retinoblastoma-effect of melphalan on in vitro electroretinogram. Nippon Ganka Gakkai Zasshi 98(4):352–356
Ueda M, Tanabe J, Inomata M, Kaneko A, Kimura T (1995) Study on conservative treatment of retinoblastoma-effect of intravitreal injection of melphalan on the rabbit retina. Nippon Ganka Gakkai Zasshi 99(11):1230–1235
Okabe J, Kimura H, Kunou N, Okabe K, Kato A, Ogura Y (2003) Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate. Invest Ophthalmol Vis Sci 44(2):740–744
Marmor MF, Holder GE, Seeliger MW, Yamamoto S (2004) Standard for clinical electroretinography (2004 update). Doc Ophthalmol 108(2):107–114
Shields JA, Shields CL (1990) Treatment of retinoblastoma with cryotherapy. Trans Pa Acad Ophthalmol Otolaryngol 42:977–980
Rosengren B, Tengroth B (1977) Retinoblastoma treated with a 60CO applicator. Acta Radiol Ther Phys Biol 16(2):110–116
Shields CL, Shields JA, Minelli S, De Potter P, Hernandez C, Cater J, Brady L (1993) Regression of retinoblastoma after plaque radiotherapy. Am J Ophthalmol 115(2):181–187
Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, Seddon J, Tarbell N, Boice JD Jr (1997) Mortality from second tumors among long-term survivors of retinoblastoma. J Natl Cancer Inst 85(14):1121–1128
Shields CL, Shields JA, Needle M, de Potter P, Kheterpal S, Hamada A, Meadows AT (1997) Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology 104(12):2101–2111
Friedman DL, Himelstein B, Shields CL, Shields JA, Needle M, Miller D, Bunin GR, Meadows AT (2000) Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. J Clin Oncol 18(1):12–17
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Grant Support: Supported in part by a grant from the Health and Welfare Ministry, Japan.
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Shimoda, Y., Hamano, R., Ishihara, K. et al. Effects of intraocular irrigation with melphalan on rabbit retinas during vitrectomy. Graefes Arch Clin Exp Ophthalmol 246, 501–508 (2008). https://doi.org/10.1007/s00417-007-0685-3
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DOI: https://doi.org/10.1007/s00417-007-0685-3