Retinoblastoma is the most common primary malignant ocular malignancy in children. The management and treatment of retinoblastoma is a very complex process and requires attention to different aspects, such as the stage of the disease based on the International classification of retinoblastoma (ICRB) or International intraocular retinoblastoma classification (IIRC), the genetic status of the tumor and mutations, psycho-social factors of the family and society, cultural beliefs, and available economic resources. From the identification of this malignancy until the beginning of the 20th century (before the introduction of radiation therapy as one of the treatment options), enucleation was the only treatment option for this disease. In addition to not controlling metastatic and extensive features of the disease and increasing the chance of death in these cases, enucleation causes many adverse psychological and aesthetic complications in patients, and especially children, who are the main population affected by this disease. Tremendous progress has been made since the 20th century to identify and invent new methods to preserve the eyes and less invasive treatments (globe salvage treatments), and the set of efforts led to the inventing of new treatment methods such as radiation therapy, systemic chemotherapy, local treatments such as cryotherapy and thermotherapy, intra-arterial chemotherapy and intraocular chemotherapy. In summary, the set of treatments from the beginning until now has gone towards increasing survival, reducing the rate of enucleation and providing more targeted and less invasive treatments. Despite these advances, early diagnosis is the most important prerequisite for better outcomes. However, early detection is influenced by socioeconomic factors and is a major challenge, especially in low- and middle-income countries. In fact, the provision of advanced medical care in high-income areas has provided excellent survival, globe, and vision-saving rates. Unfortunately, these results do not hold true for medical systems in low- and middle-income areas, leading to poor patient outcomes. In this article, we briefly introduce various retinoblastoma treatment methods from the beginning of detection until now, and we assess the evolution of the treatment of this disease from the beginning until now, which has reduced the need for enucleation as a treatment for this disease.
