Intravitreal Chemotherapy

Studies suggest that direct intravitreal injection of melphalan or topotecan may be effective in controlling active vitreous seeds.[46,47]; [48,49][Level of evidence C2] A retrospective study of 264 eyes (250 children) treated with intravitreal melphalan for vitreous seeds over a two-decade period reported a complete remission rate of 68%. There was a low incidence of extraocular spread as a result of the injection that occurred in children with high-risk features.[50][Level of evidence C2]

Because of initial concerns about the potential for tumor dissemination, the use of intravitreal chemotherapy was limited. However, additional reports have estimated that the proportion of patients with extraocular tumor spread, as the result of intravitreal injection, is negligible.[51,52] While this procedure is safe and well tolerated, recent studies have shown a direct correlation between the number of injections and a decrease in retinal function, as measured by ERG.[52]; [53][Level of evidence C3]

Preliminary data support that intra-arterial chemotherapy plus intravitreal chemotherapy (as needed for vitreous seeding) may improve globe salvage in eyes with advanced retinoblastoma when compared with children who were treated in earlier years with intra-arterial chemotherapy alone.[52]; [32][Level of evidence C2] Compared with the children treated in the earlier era, children treated in the later era received a combination of intra-arterial and intra-vitreal chemotherapy, which demonstrated shorter time to regression, fewer recurrences, fewer enucleations, and no increased toxicity, including no difference in loss of retinal function as measured by ERG.[33][Level of evidence C3]

As experience with the use of intra-vitreal chemotherapy expands, studies have demonstrated its efficacy in controlling subretinal seeds and recurrent retinal tumors, suggesting a potential role beyond the control of vitreous seeds as an adjunctive therapy in the globe-sparing treatment of retinoblastoma.[54]