Abstract
The aim of this study is to evaluate the pathological findings of the eye after intravitreal melphalan for viable vitreous seeding from retinoblastoma. All enucleated eyes receiving an intravitreal injection of melphalan (10−50 μg in 0.05 cc) were evaluated for histological changes. Of 25 treated cases, 8 eyes needed enucleation because of phthisis, parent request, or new tumor development. One of the cases was excluded from the study because of a history of intra-arterial chemotherapy with melphalan. There was no case of needle-site scleral involvement by retinoblastoma cells. In two eyes receiving 50 μg melphalan, no viable retinoblastoma cell was detectable in the eye. Severe gliosis, vascular occlusion, retinal necrosis, hemorrhage and neovascularization were seen. Histologically, intravitreal melphalan for recalcitrant or recurrent vitreous seeds from retinoblastoma appears to provide acceptable vitreous seed control. It seems that higher doses could be destructive causing ischemic necrosis in the retina, severe gliosis and secondary neovascular changes as well as having a destructive effect on retinoblastoma cells.
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Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA (2006) The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology 113:2276–2280
Abramson DH, Ellsthworth RM, Tretter P, Adams K, Kitchin FD (1981) Simultaneous bilateral radiation for advanced bilateral retinoblastoma. Arch Ophthalmol 99:1763–1766
Shields CL, Shields JA, De Potter P, Minelli S, Hernandez C, Brady LW, Cater JR (1993) Plaque radiotherapy in the management of retinoblastoma. Ophthalmology 100:216–224
Shields CL, Bianciotto CG, Jabbour P, Ramasubramanian A, Lally SE, Griffin GC, Rosenwasser R, Shields JA (2011) Intra-arterial chemotherapy for retinoblastoma. Report no. 1: control of tumor, subretinal seeds, and vitreous seeds. Arch Ophthalmol 129:1399–1406
Wilson MW, Qaddoumi I, Billups C, Haik BG, Rodriguez-Galindo C (2011) A clinicopathological correlation of 67 eyes primarily enucleated for advanced intraocular retinoblastoma. Br J Ophthalmol 95:553–558
Ericson LA, Rosengren BH (1961) Present therapeutic resources in retinoblastoma. Acta Ophthalmol 39:569–576
Kaneko A (1996) Teach us about the current treatments of retinoblastoma. Atarashii Ganka 13:229–233 (in Japanese)
Kivelä T, Eskelin S, Paloheimo M (2011) Intravitreal methotrexate for retinoblastoma. Ophthalmology 118:1689
Munier FL, Gaillard MC, Balmer A, Soliman S, Podilsky G, Moulin AP, Beck-Popovic M (2012) Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol 96:1078–1083
Ghassemi F, Shields CL (2012) Intravitreal melphalan for refractory or recurrent vitreous seeding from retinoblastoma. Arch Ophthalmol 130:1268–1271
Bosaleh A, Sampor C, Solernou V, Fandiño A, Domínguez J, de Dávila MT, Chantada GL (2012) Outcome of children with retinoblastoma and isolated choroidal invasion. Arch Ophthalmol 130:724–729
Ericson LA, Kalberg B, Rosengren BH (1964) Trials of intravitreal injections of chemotherapeutic agents in rabbits. Acta Ophthalmol 42:721–726
Inomata M, Kaneko A (1987) Chemosensitivity profiles of primary and cultured retinoblastoma cells in a human tumor clonogenic assay. Jpn J Cancer Res 78:858–868
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. J Jpn Ophthalmol Soc 99:1230–1235 (in Japanese)
Steinle JJ, Zhang Q, Thompson KE, Toutounchian J, Yates CR, Soderland C, Wang F, Stewart CF, Haik BG, Williams JS, Jackson JS, Mandrell TD, Johnson D, Wilson MW (2012) Intra-ophthalmic artery chemotherapy triggers vascular toxicity through endothelial cell inflammation and leukostasis. Invest Ophthalmol Vis Sci 30(53):2439–2445
Eagle RC Jr, Shields CL, Bianciotto C, Jabbour P, Shields JA (2011) Histopathologic observations after intra-arterial chemotherapy for retinoblastoma. Arch Ophthalmol 129:1416–1421
Kim J, Do H, Egbert P (2011) Enucleated eyes after failed intra-arterial infusion of chemotherapy for unilateral retinoblastoma: histopathologic evaluation of vitreous seeding. Clin Ophthalmol 5:1655–1658
Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP (2008) A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology 115:1398–1404
Vajzovic LM, Murray TG, Aziz-Sultan MA, Schefler AC, Fernandes CE, Wolfe SC, Hess DJ, Dubovy SR (2010) Clinicopathologic review of enucleated eyes after intra-arterial chemotherapy with melphalan for advanced retinoblastoma. Arch Ophthalmol 128:1619–1623
Graeber CP, Gobin YP, Marr BP, Dunkel IJ, Brodie SE, Bornfeld N, Char DH, Folberg R, Imhof SM, Lin AY, Berry JL, Al Mesfer S, Moll AC, Abramson DH (2011) Histopathologic findings of eyes enucleated after treatment with chemosurgery for retinoblastoma. Open Ophthalmol J 5:1–5
Bechrakis NE, Bornfeld N, Schueler A, Coupland SE, Henze G, Foerster MH (1998) Clinicopathologic features of retinoblastoma after primary chemoreduction. Arch Ophthalmol 116:887–893
Dithmar S, Aabert TM Jr, Grossniklaus HE (2000) Histopathologic changes in retinoblastoma after chemoreduction. Retina 20:33–36
Demirci H, Eagle RC Jr, Shields CL, Shields JA (2003) Histopathologic findings in eyes with retinoblastoma treated only with chemoreduction. Arch Ophthalmol 121:1125–1131
Munier FL, Beck-Popovic M, Balmer A, Gaillard MC, Bovey E, Binaghi S (2011) Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma. Retina 31:566–573
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Ghassemi, F., Amoli, F.A. Pathological findings in enucleated eyes after intravitreal melphalan injection. Int Ophthalmol 34, 533–540 (2014). https://doi.org/10.1007/s10792-013-9851-2
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DOI: https://doi.org/10.1007/s10792-013-9851-2