Background/aims To review the effectiveness of intra-arterial chemotherapy for advanced intra-ocular retinoblastoma with vitreous and/or subretinal seeds in naive (untreated) and previously treated eyes. Methods Retrospective study, approved by the institutional review board, of 76 eyes of 67 patients with retinoblastoma with subretinal and/or vitreous seeding treated with intra-arterial chemotherapy at Memorial Sloan-Kettering Cancer Center between May 2006 and August 2010. Results Despite advanced intraocular disease with seeding, the majority (56/76) of eyes were saved; 20/76 eyes were enucleated. Among treatment-naive eyes, the 2-year probability of ocular salvage was 83% (95% CI 27% to 97%) for eyes with subretinal seeding only, 64% (95% CI 24% to 87%) for eyes with vitreous seeding only, and 80% (95% CI 40% to 95%) for eyes with both. Among eyes that received previous treatment and had progressed, the 2-year probability of ocular salvage was 50% (95% CI 15% to 78%) for eyes with only subretinal seeding, 76% (95% CI 48% to 91%) for eyes with vitreous seeding only, and 54% (95% CI 20% to 79%) for eyes with both. Nine of 29 naive eyes (31%) were cured with intra-arterial (super-selective ophthalmic artery infusion of chemotherapy) chemotherapy alone. Conclusion Unlike radiation or systemic chemotherapy, intra-arterial chemotherapy can usually prevent the need for enucleation in naive eyes with advanced intraocular retinoblastoma with seeding—especially if the seeding is subretinal. Treatment appears to be less effective in previously treated eyes when subretinal seeding is present (50% at 2 years), but may be more effective in eyes that failed to respond to previous systemic chemotherapy and have only vitreous seeding.

The management of retinoblastoma, the most common intraocular malignancy in children, has changed drastically over the last decade. Landmark developments in local drug delivery, namely, safer techniques for intravitreal chemotherapy injection and ophthalmic artery chemosurgery, have resulted in eye globe salvages that were not previously attainable using systemic chemotherapy or external beam irradiation. Novel drugs, oncolytic viruses, and immunotherapy are promising approaches in the treatment of intraocular retinoblastoma. Importantly, emerging studies of the pattern of tumor dissemination and local drug delivery may provide the first steps toward new treatments for metastatic disease. Here, we review recent advances in retinoblastoma treatment, especially with regard to local drug delivery, that have enabled successful conservative management of intraocular retinoblastoma. We also review emerging data from preclinical and clinical studies on innovative approaches that promise to lead to further improvement in outcomes, namely, the mechanisms and potential uses of new and repurposed drugs and non-chemotherapy treatments, and discuss future directions for therapeutic development.

Retinoblastoma has gone from >95% mortality to >95% survival in the past 100 years. Once enucleation techniques were perfected, the majority of children survived, but without the eye (or vision in that eye). Over the past 100 years, progressively better techniques have been developed for salvaging vision without sacrificing patient survival. Presently, 99% of children treated at our center survive their cancer, >99% retain at least one eye, and >90% retain normal vision in at least one eye. The introduction of ophthalmic artery chemosurgery has been the most dramatic, non-radiation-based mode to maximally preserve vision.

Case Report from JAMA Ophthalmology — Bilateral Superselective Ophthalmic Artery Chemotherapy for Bilateral Retinoblastoma — Tandem Therapy