Intravenous Chemotherapy for Retinoblastoma in the Era of Intravitreal Chemotherapy: A Systematic Review

Purpose: The published data on ocular survival following intravenous chemotherapy of retinoblastoma (RB) seems to be skewed by evolving practice patterns induced by use of intravitreal chemotherapy (iVitc). We aimed to explore potential role of iVitc for vitreous seeding for patients treated with intravenous chemotherapy (IVC). Methods: A literature search was performed to identify cases of RB treated with primary IVC prior to advent of iVitc by various search engines (PubMed, Medline, and Google) from 1992 to 2018. Studies were excluded if number of cases were less than 40 or lacked data related to type of recurrence and its treatment. Rates and patterns of recurrence and its management were categorized. Results: Out of 15 studies identified, only 10 studies (797 eyes) met the inclusion criteria. The mean age at presentation was 15.3 months (range 0–192.8 months). Unilateral cases represented 25% of the cohort. The ocular survival rate with primary IVC was 63% (500/797 eyes). Of the 297 eyes (37%) that failed IVC therapy, additional 99 eyes could be salvaged with EBRT (599/797 eyes, 75%). Remaining 198 eyes were enucleated (198/797 eyes 25%). K-M survival analysis could not be done due lack of sufficient data. Recurrences that occurred (mean 12.2 months) after completion of primary IVC included relapse of retinal tumor (143 eyes [48%]), vitreous seeding (73 eyes [25%]), subretinal seeding (49 eyes [16%]), or any combination (103 eyes [35%]). Out of 73 eyes with vitreous seeding, additional 66 eyes (90%) would have been salvaged with iVitc, potentially improving ocular survival rates to 71% (500 + 66/797). Conclusions: Evolving practice patterns of RB treatment have unfavorably skewed published ocular survival rates following IVC. With incorporation of iVitc, the ocular survival rates with IVC can be potentially improved to be non-inferior to those achieved with intra-arterial chemotherapy.