The history of human treatment of RB has been 200 years, and in 1809 the Scottish physician James Wardrop pioneered the surgical treatment of RB, while ophthalmopexy became the only and standard method of treatment for RB in the world in the 19th and 20th centuries, and in most areas of China it continues even today. 1921 Dr. Verhoeff in the United States pioneered the successful treatment of RB with radiation therapy, In 1921, Dr. Verhoeff in the United States pioneered the successful treatment of RB, making eye removal and external radiation therapy the two cornerstones of RB treatment in the world for more than half a century. Professors Reese and Ellsworth were the leaders in RB treatment during this period, and in 1963 they developed the widely used Reese-Ellsworth (RE) grading scale for intraocular stage RB. In 1993, their student, Dr. Abramson, found that some (35%) of the patients developed other malignancies (second malignancies) several years later through follow-up of long-term RB survivors. There were at least 23 histological types, the most common of which was osteogenic sarcoma. Although the development of second malignancies is thought to be primarily genetic, early (less than 12 months of age) external radiation therapy in patients with genetic RB can significantly increase the incidence of second malignancies. Once the second malignancy occurs, the prognosis is very poor. External radiation therapy can also cause significant orbital malformations. This result has led several major international RB treatment centers to experiment with systemic chemotherapy in the management of RB, which is why there has been a major change in the international concept of RB treatment over the past decade. Now, chemotherapy combined with multiple aggressive local treatments is gradually rising to first-line treatment, while external radiation therapy is relegated to second-line treatment and ophthalmic removal to third-line treatment. This change is considered to be a new era in RB treatment. Since the factors affecting the effectiveness of external radiation therapy are mainly the location, number and size of tumors, the RE classification of RB is mainly used to evaluate the effectiveness of external radiation therapy and is less predictive of the efficacy of chemotherapy. The factors affecting the effect of chemotherapy combined with multiple active local treatments are no longer the location, number and size of the tumor, but mainly the dispersed implantation of RB cells in the vitreous and subretinal cavity. It was established as the international classification standard for intraocular phase RB (ICRB) by experts from various countries at the 11th International Conference on RB in Paris in 2003. According to reports from several RB treatment centers abroad since 1996, chemotherapy alone does not completely cure RB, but often results in significant reduction in tumor size, secondary retinal detachment, and metastasis, thus allowing for local treatment. This is why chemotherapy is sometimes referred to as chemoreduction. In hereditary RB, chemotherapy can also prevent the development of new tumor foci and second malignancies (especially intracranial trilateral RB). Commonly used drugs include vincristine, etoposide, carboplatin, cyclophosphamide, cyclosporine A, etc. The commonly used regimen is the VEC regimen, which is a combination of vincristine, etoposide, and carboplatin applied for 6 courses of 2 d each, with an interval of 3-4 weeks between courses. Since RB is highly susceptible to resistance, it can sometimes be reversed by adding a high dose of cyclomycin A for a short period of time. Fundus examination (EUA) under general anesthesia is performed 1 to 3 d before each course of treatment to record changes in the disease, and retinal cryotherapy is performed to increase the accumulation of chemotherapeutic drugs in the eye. In general, the tumor shrinks significantly after 2-3 courses, and then local treatment (such as laser photocoagulation, cryotherapy, transpupillary thermotherapy, superficial scleral patch radiotherapy) is started at the same time as EUA. After 6 courses, EUA should be performed every 3-6 weeks to record the change of disease or local treatment. The interval of EUA should be gradually extended after the disease stabilization. This regimen has been reported to save 100% of ICRB grade A, 93% of ICRB grade B, 90% of ICRBC grade, and 47% of ICRB grade D RB patients from external radiation therapy and eye removal, but is less effective for tumor cells disseminated in the vitreous cavity and subretinal space. For RB in extraocular and systemic metastatic stages, chemotherapy is often combined with surgical treatment (including removal of the eye and orbital contents) and external radiation therapy. In cases with choroidal, scleral and sieve plate metastases, chemotherapy can prevent further metastases to the whole body. For RB with systemic metastasis, high-dose chemotherapy combined with autologous stem cell transplantation can be administered: first, conventional dose of chemotherapy to reduce the possible presence of tumor cells in bone marrow and blood; then hematopoietic stem cells are collected from bone marrow or blood for freezing; then high-dose chemotherapy is administered, and the frozen autologous stem cells are returned to restore the suppressed hematopoietic system. Chemotherapy often has systemic side effects and should be administered clinically in cooperation with pediatricians and oncologists, as well as with nurse specialists. Etoposide may be associated with secondary leukemia in some patients. Sixteen cases of acute leukemia following systemic chemotherapy have recently been reported worldwide. In view of the systemic side effects of chemotherapy, clinical resistance issues, and problems leading to secondary leukemia, international colleagues have actively explored local chemotherapy (interventional therapy). The earliest work came from Japan. Due to cultural ties, in Japan, families of affected children could not accept the removal of their eyeballs to save their lives, preferring that their children leave with untreated RB. Such a reality prompted Japanese medical practitioners to actively explore ways to improve the efficacy of chemotherapy and reduce systemic side effects. They developed an interventional technique for local chemotherapy in which a balloon catheter is used to obstruct the blood supply to the brain over the fornix of the internal carotid artery, and then the proximal end of the balloon is infused with chemotherapeutic agents via the catheter, forcing the bulk of the chemotherapeutic agent directly into the ophthalmic artery, which acts as a local chemotherapy. This technique achieved good results, but because of the presence of a large number of branches and side branches of the intracranial vessels, the brain as well as the peripheral vascular branches still received high concentrations of chemotherapeutic agents. In 2006, American colleagues began to explore the possibility of inserting a microcatheter directly into the ophthalmic artery for local infusion of chemotherapy, which would allow the tumor to be treated locally with extremely high doses of chemotherapeutic agents while the whole body would receive very little, and in 2008 they reported exciting results. Interventional treatment of retinoblastoma will be an extremely promising treatment, especially for children with intraocular stages, and is expected to replace conventional systemic chemotherapy.