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.

Intravitreal bevacizumab remarkably augmented the short-term response to scatter panretinal laser photocoagulation in high-risk characteristic proliferative diabetic retinopathy but the effect was short-lived, as many of the eyes showed rapid recurrence. Alternative dosing (multiple and/or periodic intravitreal Avastin injections) is recommended for further evaluation.

Single intravitreal bevacizumab or triamcinolone plus bevacizumab injection brought about significantly greater macular thickness reduction in diabetic patients in comparison to standard laser treatment. However, the response for bevacizumab alone was short-lived. Reduction in macular thickness was only marginally associated with visual acuity improvement in the triamcinolone plus bevacizumab injection group.

The authors observed a relatively high incidence of ROP in this series, especially its severe form affecting relatively more mature infants, which merits further investigation. GA, BW and oxygen therapy were independent ROP determinants.

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Recurrence of neovascularization with bevacizumab monotherapy seems to be higher than that with conventional laser therapy among infants with Type 1 ROP in zone II ROP but reinjection of bevacizumab causes regression in most recurrent cases.

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