Retinoblastoma is the most common ocular neoplasm in children. Left untreated it spreads to the brain via the optic nerve. Traditional therapy is enucleation, and while this procedure is still the most common treatment worldwide, modern eye-preserving therapies can often spare the globe. However, patients with retinoblastoma often present in advanced stages of the disease when these globe-preserving strategies are often insufficient to prevent enucleation. In these challenging cases, direct infusion of chemotherapy into the ophthalmic artery has been attempted to achieve tumor control. The authors' aim in this study was to report on their initial experience with and clinical results for this approach.

The authors prospectively collected data on all cases of retinoblastoma treated with selective intraophthalmic melphalan at Bascom Palmer Eye Institute. All cases were classified as International Intraocular Retinoblastoma Classification (IIRC) Group D or Reese-Ellsworth Group Vb, had not responded to aggressive multimodal therapy consisting of chemotherapy and focal consolidating laser therapy, and were pending enucleation. Using digital subtraction angiography, a microcatheter was navigated under roadmap guidance into the ophthalmic artery, and melphalan was infused over 40 minutes. Early in the series, patients were treated with 3 or 5 mg of melphalan, but after low response rates occurred all eyes were treated with 7.5 mg of melphalan. All patients were examined with funduscopy while under anesthesia 3 weeks after treatment and every 3 months thereafter. Patients with persistent disease were retreated with repeat infusions of melphalan.

Twenty-six procedures were performed to treat 17 tumors in 15 patients. Successful cannulation of the ophthalmic artery was achieved in all cases. The follow-up ranged from 3 to 12 months, with a mean of 8.6 months. Overall, 76% of the tumors responded to therapy and these cases were spared enucleation. The average number of treatments was 1.5 per tumor. Of the responders, 54% responded to a single dose of melphalan. Treatment with the higher dose of 7.5 mg up front was associated with a lower enucleation rate (0% vs 36%) as compared with the lower starting dose. Delayed vitreous hemorrhage occurred after 4 (15%) of 26 treatments, and these cases were treated with enucleation.

In this challenging group of advanced retinoblastomas refractory to aggressive multimodal therapy, virtually 100% of eyes are generally enucleated. In contrast, the authors' protocol of infusing melphalan directly into the ophthalmic artery led to a dramatic decrease in the enucleation rate to 23.5%. While it is now the treatment of choice for refractory retinoblastoma at their center, its role in less advanced disease remains to be elucidated.