Abstract
The clinical heterogeneity of vitreous seeds can be distinguished into three classes (dust, spheres, and clouds). New evidence suggests that this classification system can be predictive of response to intravitreal melphalan.
Historically, intravitreal injections of chemotherapy have been avoided in retinoblastoma eyes, due to concerns regarding risk of extraocular dissemination. However, these fears have been allayed by a low reported incidence of spread along the needle tract. The low risk has been attributed to an evolution in the injection method and the implementation of safety enhancing techniques. Discussed here are the various methods that have been adopted and the rationale for their use.
While intravitreal injections have been deemed to be relatively safe, they are not without consequences to the eye. Summarized here are the clinical and preclinical findings of clinical toxicity and retinal toxicity as measured by electroretinogram (ERG). There is compelling evidence to suggest that each intravitreal injection of melphalan results in a measurable degradation in electroretinogram, and over the average injection course, this may result in up to a 30 % loss of normal retinal function as measured by ERG. While intravitreal injections of melphalan are now saving eyes that historically would have been lost to enucleation, there are still questions regarding the toxicity of this technique and how this correlates to visual function.
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References
Chévez-Barrios P, Chintagumpala M, Mieler W, Paysse E, Boniuk M, Kozinetz C, et al. Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir. J Clin Oncol. 2005;23(31):7927–35.
Dunkel IJ, Shi W, Salvaggio K, Marr BP, Brodie SE, Gobin YP, et al. Risk factors for severe neutropenia following intra-arterial chemotherapy for intra-ocular retinoblastoma. PLoS One. 2014;9(10), e108692.
Ericson LA, Rosengren BH. Present therapeutic resources in retinoblastoma. Acta Ophthalmol. 1961;39:569–76.
Francis JH, Schaiquevich P, Buitrago E, Del Sole MJ, Zapata G, Croxatto JO, et al. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study. Ophthalmology. 2014a;121(9):1810–7.
Francis JH, Xu XL, Gobin YP, Marr BP, Brodie SE, Abramson DH. Death by water: precautionary water submersion for intravitreal injection of retinoblastoma eyes. Open Ophthalmol J. 2014b;8:7–11.
Francis JH, Marr BP, Brodie SE, Gobin YP, Abramson DH. Tethered vitreous seeds following intravitreal melphalan for retinoblastoma. JAMA Ophthalmol. 2014c;132(8):1024–5.
Francis JH, Abramson DH, Gaillard M-C, Marr BP, Beck-Popovic M, Munier FL. The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan. Ophthalmology. 2015. doi:10.1016/j.ophtha.2015.01.017
Ghassemi F, Amoli FA. Pathological findings in enucleated eyes after intravitreal melphalan injection. Int Ophthalmol. 2014;34(3):533–40.
Ghassemi F, Shields CL. Intravitreal melphalan for refractory or recurrent vitreous seeding from retinoblastoma. Arch Ophthalmol. 2012;130(10):1268–71.
Ghassemi F, Shields CL, Ghadimi H, Khodabandeh A, Roohipoor R. Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma. JAMA Ophthalmol. 2014;132(8):936–41.
Henkes HE, Manschot WA. The danger of diagnostic biopsy in eyes suspected of an intraocular tumour. Ophthalmologica. 1963;145:467–9.
Inomata M, Kaneko A. Chemosensitivity profiles of primary and cultured human retinoblastoma cells in a human tumor clonogenic assay. Jpn J Cancer Res. 1987;78(8):858–68.
Kaneko A, Suzuki S. Eye-preservation treatment of retinoblastoma with vitreous seeding. Jpn J Clin Oncol. 2003;33(12):601–7.
Karcioglu ZA. Fine needle aspiration biopsy (FNAB) for retinoblastoma. Retina. 2002;22(6):707–10.
Kivelä T, Eskelin S, Paloheimo M. Intravitreal methotrexate for retinoblastoma. Ophthalmology. 2011;118(8):1689; e1–6.
Lee V, Hungerford JL, Bunce C, Ahmed F, Kingston JE, Plowman PN. Globe conserving treatment of the only eye in bilateral retinoblastoma. Br J Ophthalmol. 2003;87(11):1374–80.
Munier FL. Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013. Ophthalmic Genet. 2014;35(4):193–207.
Munier FL, Soliman S, Moulin AP, Gaillard M-C, Balmer A, Beck-Popovic M. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track. Br J Ophthalmol. 2012a;96(8):1084–7.
Munier FL, Gaillard M-C, Balmer A, Soliman S, Podilsky G, Moulin AP, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol. 2012b;13.
Munier FL, Gaillard M-C, Balmer A, Beck-Popovic M. Intravitreal chemotherapy for vitreous seeding in retinoblastoma: recent advances and perspectives. Saudi J Ophthalmol. 2013;27(3):147–50.
Suzuki S, Kaneko A. Vitreous injection therapy of melphalan for retinoblastoma. XVth Biannual Meeting, International Society of Ocular Oncology. 2011; Buenos Aires, Argentina.
Seregard S, Kock E, af Trampe E. Intravitreal chemotherapy for recurrent retinoblastoma in an only eye. Br J Ophthalmol. 1995;79(2):194–5.
Shimoda Y, Hamano R, Ishihara K, Shimoda N, Hagimura N, Akiyama H, et al. Effects of intraocular irrigation with melphalan on rabbit retinas during vitrectomy. Graefes Arch Clin Exp Ophthalmol. 2008;246(4):501–8.
Smith SJ, Smith BD. Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma: a systematic review. Br J Ophthalmol. 2013;5.
Smith SJ, Pulido JS, Salomão DR, Smith BD, Mohney B. Combined intravitreal and subconjunctival carboplatin for retinoblastoma with vitreous seeds. Br J Ophthalmol. 2012;96(8):1073–7.
Smith SJ, Smith BD, Mohney BG. Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review. Br J Ophthalmol. 2014;98(3):292–7.
Ueda M, Tanabe J, Inomata M, Kaneko A, Kimura T. Study on conservative treatment of retinoblastoma—effect of intravitreal injection of melphalan on the rabbit retina. Nippon Ganka Gakkai Zasshi. 1995;99(11):1230–5.
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Jasmine H. Francis declares that she has no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Memorial Sloan Kettering Cancer Center) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed.
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Francis, J.H. (2015). Vitreous Disease and the Technique, Safety and Toxicity of Intravitreal Chemotherapy for Retinoblastoma. In: Francis, J., Abramson, D. (eds) Recent Advances in Retinoblastoma Treatment. Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-319-19467-7_4
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DOI: https://doi.org/10.1007/978-3-319-19467-7_4
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