the size, location, and multi-focality of the tumor. the system was originally used to decide the best treatment result by using external beam radiotherapy, as well as, the likeliness of salvaging the globe of the eye. due to chemotherapy not being part of the reese ellsworth classification system, there needed to be an updated classification system to foresee the treatment outcomes of chemotherapy. the international classification for intraocular retinoblastoma is now the current system being used, and it was created by murphree and associates. according to reese and ellsworth, there were different groups that had various features in order to classify the globe salvage as very favorable to the category of very unfavorable. in order to salvage the affected eye, the disc diameter had to be around 4dd and behind the equator to have higher favorability. if the tumor was around ten in disc diameter and involved roughly 50% of the retina, it was considered unfavorable to salvage the globe which could result in enucleation. according to murphree, the different groups were classified from very low risk to very high risk which was determined by features of the given tumor. very low risk means that the tumor has to be less than 3mm and there must be no seeding of the vitreous or sub-retinal area. when a patient is very high risk, the tumor presents itself with multiple features and is going to have to be treated with conservative treatment modalities or enucleation. group clinical features a very low risk all tumors are 3mm or smaller, confined to the retina, and located at least 3mm from the foveola and 1.5mm from the optic nerve. no vitreous or subretinal seeding b low risk retinal tumors may be any size or location not in group a, no vitreous or subretinal seeding allowed. a small cuff of subretinal fluid extending no more than 5mm from the base of the tumor is allowed c moderate risk eyes with only focal vitreous or subretinal seeding and discrete retinal tumors of any size and location. vitreous or subretinal seeding may extend no more than 3mm from the tumor. up to one quadrant of subretinal fluid may be present d high risk eyes with diffuse vitreous or subretinal seeding and/or massive, nondiscrete endophytic or exophytic disease. more than one quadrant of retinal detachment e very high risk eyes eyes with one or more of the following: irreversible neovascular glaucoma massive intraocular hemorrhage aseptic orbital cellulitis phthisis or pre-phthisis tumor anterior to anterior vitreous face tumor touching the lens diffuse infiltrating retinoblastoma international classification for intraocular retinoblastoma treatment historical image showing gordon isaacs, the first patient treated with the linear accelerator (external beam radiation therapy) for retinoblastoma, in 1957. gordon's right eye was removed january 11, 1957 because the cancer had spread. his left eye, however, had only a localized tumor that prompted henry kaplan to try to treat it with the electron beam. the priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. the exact course of treatment depends on the individual case and is decided by the ophthalmologist in discussion with the paediatric oncologist. correct treatment also depends on the mutation type, whether it is a germline rb1 mutation, a sporadic rb1 mutation or mycn amplification with functional rb1. children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies). the various treatment modalities for retinoblastoma includes: enucleation of the eye – most patients with unilateral disease present with advanced intraocular disease, so usually undergo enucleation, which results in a cure rate of 95%. in bilateral rb, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision. external beam radiotherapy (ebrt) – the most common indication for ebrt is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of chemotherapy and local therapies. however, patients with hereditary disease who received ebrt therapy are reported to have a 35% risk of second cancers. brachytherapy involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. it used as the primary treatment, or more frequently, in patients with small tumors or in those who had failed initial therapy including previous ebrt therapy. thermotherapy involves the application of heat directly to the tumor, usually in the form of infrared radiation. it is also used for small tumors. laser photocoagulation is recommended only for small posterior tumors. an argon or diode laser or a xenon arc is used to coagulate all the blood supply to the tumor. cryotherapy induces damage to the vascular endothelium with secondary thrombosis and infarction of the tumor tissue by rapidly freezing it. it may be used as primary therapy for small peripheral tumors or for small recurrent tumors previously treated with other methods. systemic chemotherapy has become forefront of treatment in the past decade, in the search for globe-preserving measures and to avoid the adverse effects of ebrt therapy. the common indications for chemotherapy for intraocular retinoblastoma include tumors that are large and that cannot be treated with local therapies alone in children with bilateral tumors. it is also used in patients with unilateral disease when the tumors are small, but cannot be controlled with local therapies alone. intra-arterial chemotherapy – chemotherapeutic drugs are administered locally by a thin catheter threaded through the groin, through the aorta, and the neck, directly into the optic vessels. nanoparticulate chemotherapy – to reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents (carboplatin) has been developed, which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects. chemoreduction is a combined approach using chemotherapy to initially reduce the size of the tumor, and adjuvant focal treatments, such as transpupillary thermotherapy, to control the tumor. prognosis in the developed world, retinoblastoma has one of the best cure rates of all childhood cancers (95-98%), with more than 90% of sufferers surviving into adulthood. in the uk, around 40 to 50 new cases are diagnosed each year. good prognosis depends upon early presentation of the child in health facility. late presentation is associated with a poor prognosis. survivors of hereditary retinoblastoma have a higher risk of developing other cancers later in life. epidemiology retinoblastoma presents with cumulative lifetime incidence rate of one case of retinoblastoma per 18000 to 30000 live births worldwide. a higher incidence is noted in developing countries, which has been attributed to lower socioeconomic status and the presence of human papilloma virus sequences in the retinoblastoma tissue. almost 80% of children with retinoblastoma are diagnosed before three years of age and diagnosis in children above six years of age is extremely rare. in the uk, bilateral cases usually present within 14 to 16 months, while diagnosis of unilateral cases peaks between 24 and 30 months.