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  • Title: Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma.
    Author: Ghassemi F, Shields CL, Ghadimi H, Khodabandeh A, Roohipoor R.
    Journal: JAMA Ophthalmol; 2014 Aug; 132(8):936-41. PubMed ID: 24789622.
    Abstract:
    IMPORTANCE: Demonstrating the usefulness and complications of multiagent intravitreal chemotherapy is necessary for successful treatment in patients with recalcitrant vitreous seeding of retinoblastoma. OBJECTIVE: To determine the efficacy and complications of combined intravitreal chemotherapy (melphalan hydrochloride and topotecan hydrochloride) for viable vitreous seeding from retinoblastoma. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study was conducted in a hospital setting. Trans-pars plana intravitreal injection of melphalan hydrochloride (40 µg in 0.04 mL of diluent) combined with topotecan hydrochloride (8-20 µg in 0.04 mL of balanced salt solution) was performed in 9 eyes, followed by injection site cryotherapy. MAIN OUTCOMES AND MEASURES: Complete regression of vitreous seeds of retinoblastoma. RESULTS: Nine eyes, initially classified as group D (n = 6) or E (n = 3) according to International Classification of Retinoblastoma categorization, received a standard 6 cycles of intravenous chemotherapy and/or intra-arterial chemotherapy and subsequently developed recurrent viable vitreous seeds. Intravitreal administration of melphalan combined with topotecan produced complete control of vitreous seeds in all 9 eyes following a mean of 1.9 injections (median, 2; range, 1-3 injections). In 3 cases (33%), tumor control was achieved with a single injection, whereas in 6 (67%) cases, 2 or 3 injections were necessary. Three patients (33%) subsequently underwent enucleation because of recurrent tumor and persistent anterior chamber lesions. During a mean 15.2 months of follow-up (median, 16; range, 7-25 months), there was no recurrence of new tumor or vitreous seeds in the remaining 6 eyes. Complications included temporary hypotonia of 2 weeks or less (2 [22%]), temporary epithelial defect (1 [11%]), and vitreous hemorrhage (1 [11%]). There was no case of episcleral or orbital retinoblastoma extension or remote retinoblastoma metastasis. There was no change in the a and b waves of bright-flash electroretinograms. CONCLUSIONS AND RELEVANCE: Administration of combined intravitreal melphalan and topotecan in eyes not subsequently enucleated appears to be safe and effective for resistant or recurrent vitreous seeds from retinoblastoma. In 3 of the cases (33%), tumor control was achieved with a single injection.
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