**4. Intravitreal chemotherapy for retinoblastoma**

Intravitreal chemotherapy (IVitC) is another well-established targeted therapy accounting for one of the important current treatment modalities for retinoblastoma manifesting vitreous seeds. Initial reports on IVitC date back to the 1960s where thiotepa was injected into the vitreous cavity of six eyes with retinoblastoma; yet the results were inconclusive due to the limited number of treated eyes [56]. Later, this method was revived by Kaneko and Suzuki who injected melphalan intravitreally in 41 eyes along with ocular hyperthermia to cure vitreous seeding with a notable resultant eye preservation rate of 51.3% [57]. The choice of melphalan was essentially based on in-vitro testing of 12 anti-neoplastic drugs, and melphalan proved to be the most effective against retinoblastoma cells [45]. Implementing this technique into current practice took several years and perhaps the major limiting factor was the fear of disseminating the cancer cells during injection with the risk of subsequent extraocular spread causing metastasis and death. This section will elaborate on the key qualities of this relatively new therapy.
