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Retinoblastoma (RB) therapy has evolved over decades.In the 1970s, enucleation was important for improving life prognosis.In the 1980s, external beam radiotherapy (EBRT) was popular.In the 1990s, systemic intravenous chemotherapy (IVC) was introduced and currently remains prevalent worldwide for intraocular RB control as well as prevention of systemic metastasis.However, RB seeds in vitreous and subretinal space are still the major obstacles for successful treatments.Advanced ophthalmic imaging technology promotes thorough and detailed description and observation of RB seeds.In the 2000s, interests in periocular chemotherapy (POC), intra-arterial chemotherapy (IAC) and intravitreous chemotherapy (IVitC) have been explored to overcome the low drug concentration around the seeds and to reduce the systemic side effects.This leads us into a new era of target local chemotherapy of RB.How to make the treatment decision based on biological behavior of RB seeds is a major task for us now.