Abstract
Purpose :
Intravitreal chemotherapy is an increasingly popular treatment modality for vitreous seeding in intraocular retinoblastoma. The most commonly used agent – melphalan – is associated with multiple reports of retinal toxicity. Other chemotherapeutic agents may offer similar efficacy with a more favorable safety profile
Methods :
The iRET protocol was a prospectively enrolled phase I clinical trial testing the safety and efficacy of intravitreal carboplatin in the treatment of progressive vitreous disease in intraocular retinoblastoma. Children who developed new vitreous seeds after completing primary treatment were eligible to receive an intravitreal injection of 0.3 mg carboplatin every 2 weeks. A serious adverse event prompted dose reduction to 3 µg.
Results :
Four patients were enrolled at an initial dose of 0.3 mg. Complete regression of vitreous seeds was noted in all patients following 5, 2, 2 and 1 injections. Two patients developed recurrent vitreous disease at 3 months and 25 months after complete regression. All four patients are long term survivors, but those with recurrence ultimately required enucleation. A serious adverse event occurred in one patient who developed acute vision loss with extinguished electroretinography response 72 hours after the second injection. The protocol was temporarily suspended pending dose recalculation. Two additional adverse events were noted including cataract (previously therapy included subconjunctival carboplatin exposure) and grade 3 neutropenia. Three patients were enrolled at an injection dose of 3 µg and treated with a total of 5, 2 and 1 injections respectively, with close monitoring of ERG in all cases. Complete regression of vitreous disease was not achieved in any patient at the 3 µg dose, as well as no change in ERG, but all three showed immediate clinical response to intravitreal melphalan (ocular salvage x / 3). Therefore the protocol was terminated due to lack of efficacy rather than pursue dose escalation.
Conclusions :
Intravitreal carboplatin may be effective in treating progressive vitreous seeding at higher doses. Given the occurrence of permanent retinal toxicity however, its overall therapeutic ratio appears to be unacceptably low. Other alternative agents should be investigated.
This is a 2021 ARVO Annual Meeting abstract.