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Original Investigation |

Combined Intravitreal Melphalan and Topotecan for Refractory or Recurrent Vitreous Seeding From Retinoblastoma

Fariba Ghassemi, MD1; Carol L. Shields, MD2; Hadi Ghadimi, MD1; Alireza Khodabandeh, MD1; Ramak Roohipoor, MD1
[+] Author Affiliations
1Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
2Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania
JAMA Ophthalmol. 2014;132(8):936-941. doi:10.1001/jamaophthalmol.2014.414.
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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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Figure.
Vitreous Seed Control With Combined Intravitreal Chemotherapy (Melphalan Hydrochloride and Topotecan Hydrochloride)

A, Partial vitreous seed control with 5 previous sessions of intravitreal melphalan hydrochloride, 40 µg. B, Complete vitreous seeds control with few calcified remnants, despite type 3 regression of the retinoblastoma tumor after 2 sessions of intravitreal melphalan hydrochloride, 40 µg, and topotecan hydrochloride, 20 µg, injection.

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