PurposeTo assess the effectiveness of intra-arterial chemotherapy (IAC), intravenous chemotherapy (IVC), and their combination in the management of group D retinoblastoma.MethodsThis was a retrospective, interventional, comparative, and non-randomized clinical study, including all eyes with primarily treated group D retinoblastoma managed in a single institution from February 2010 to July 2016. Patient demographics, treatment modality (primary enucleation, intravenous chemotherapy, intra-arterial chemotherapy alone or intravenous, and intra-arterial chemotherapy), additional need for consolidation treatments or intravitreal melphalan (IVM) injections, and follow-up time were recorded. The main outcome measure was ocular survival rate after various treatment modalities.ResultsOf 87 eyes of 83 consecutive cases, 9 eyes (10.3%) were primarily enucleated, 37 (42.6%) eyes received IVC, 30 (34.5%) eyes had IAC, and 11 (12.6%) eyes were treated with IVC followed by IAC. After a mean 81.175.2weeks of follow-up, enucleation rates were 56.8% in the IVC group, 23.3% in the IAC group, and 36.6% in the IVC+IAC group (p=0.021). There was no significant difference of ocular survival estimates among these 3 groups at 2 or 5years (p=0.998, p=0.986). With logistic regression analysis, age; gender; disease laterality; administration of IVM, TTT, or cryotherapy; mean dose of IVM; follow-up time; and number of IAC or IVC cycles were not significantly related to the enucleation rate (p>0.05 for all variables).Conclusions p id=Par4 Our experience showed that in group D patients, primary IAC achieved ocular survival in 76.7% of eyes, and less need for local consolidation treatments, whereas following primary IVC ocular survival was 43.2%.