AUTHOR=Yousef Yacoub A. , Al Jboor Mays , Mohammad Mona , Mehyar Mustafa , Toro Mario D. , Nazzal Rashed , Alzureikat Qusai H. , Rejdak Magdalena , Elfalah Mutasem , Sultan Iyad , Rejdak Robert , Al-Hussaini Maysa , Al-Nawaiseh Ibrahim 

TITLE=Safety and Efficacy of Intravitreal Chemotherapy (Melphalan) to Treat Vitreous Seeds in Retinoblastoma

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.696787

DOI=10.3389/fphar.2021.696787

ISSN=1663-9812

ABSTRACT=Background: Active vitreous seeds in eyes with retinoblastoma (Rb) adversely affects the treatment outcome. This study aimed to investigate the safety and efficacy of intravitreal melphalan chemotherapy (IViC) as a treatment for recurrent and refractory vitreous seeds in patients with Rb. 
Methods: A retrospective non-comparative study of patients with intraocular Rb who had vitreous seeds and treated by IViC (20-30µg of melphalan) using the safety-enhanced anti-reflux technique. Tumor response, ocular toxicity, demographics, clinical features, and survival were analyzed.
Results: Twenty-seven eyes were treated with 108 injections for recurrent (16 eyes) or refractory (11 eyes) vitreous seeds after failed systemic chemotherapy. Fifteen (56%) were males, and 20(74%) had bilateral disease. At diagnosis, majority (n=21) of the injected eyes were group D and n=6 were group C. Vitreous seeds showed complete regression in 21(78%) eyes; 100% (n=10) for eyes with focal seeds and 65% (n=11/17 eyes) for eyes with diffuse seeds (p=0.04). Seven (64%) eyes with refractory seeds and 14 (87%) eyes with recurrent seeds showed complete response (P=0.37). Sixteen (59%) eyes developed side effects; retinal toxicity (48%), pupillary synechiae (15%), cataracts (30%), iris atrophy (7%), and retinal and optic atrophy (4%). Only one child was lost to follow-up whose family refused enucleation and none developed orbital tumor recurrence or distant metastasis. 
Conclusion: IViC with melphalan is effective (more for focal than diffuse seeding) and a relatively safe treatment modality for Rb that can improve the outcomes of eye salvage procedures. However, unexpected toxicity can occur even with the standard dose of 20-30 µg.