title: Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report.
abstract: BACKGROUND
  Controlling retinoblastoma with seeding is challenging despite advances in treatment modalities. Intravitreal melphalan is an alternative to external beam radiation or enucleation for recurrent or refractory vitreous seeds. Significant ocular side effects following intravitreal melphalan injections are uncommon. Complications have been reported in eyes receiving higher concentrations of melphalan and repetitive injections. We report a case in which diffuse chorioretinal atrophy was developed at the injection site after a single, standard low-dose intravitreal melphalan injection.
  
  
  METHODS
  A 12-month-old female child without a family history of retinoblastoma presented with unilateral group C retinoblastoma in her right eye. A solitary tumour with retinal breaks on the tumour surface, and vitreous seeds overlying the tumour were observed at the 8 o'clock position of the retina. After two cycles of intra-arterial chemotherapy with melphalan, the main tumour displayed significant regression, but the vitreous seeds overlying the main tumour were still active. Because of the persistence of vitreous seeds and the inadequate response to intra-arterial melphalan treatment, intravitreal melphalan (8 μg in 0.05 mL) was injected using a 32-gauge needle 2.5 mm from the 5 o'clock position of the limbus, the meridian opposite to the vitreous seeds. After 1 month, the retina around the injection site demonstrated diffuse retinal pigment epithelium alterations with dense hard exudates. Although the main retinal mass, and vitreous seeds resolved, the hard exudates persisted for more than 2 years after the single low-dose melphalan injection.
  
  
  CONCLUSIONS
  Intravitreal melphalan injections should be cautiously used for eyes with refractory seeds, particularly when multiple injections are required to control retinoblastoma seeds. Dose- related retinal toxicity could occur in pre-treated eyes even when a relatively low standard dose is used. Such patients should be followed up closely to monitor the treatment response and to assess potential delayed toxicity.
authors.affiliation: Department of Ophthalmology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Fu-Hsin Street, Kweishan, Taoyuan, 3305, Taiwan.
authors.forename: An- Ning
authors.initials: A
authors.lastname: Chao
authors.affiliation: Department of Ophthalmology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Fu-Hsin Street, Kweishan, Taoyuan, 3305, Taiwan. kao328@cgmh.org.tw.
authors.forename: Ling-Yuh
authors.initials: LY
authors.lastname: Kao
authors.affiliation: Department of Ophthalmology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Fu-Hsin Street, Kweishan, Taoyuan, 3305, Taiwan.
authors.forename: Laura
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Fu-Hsin Street, Kweishan, Taoyuan, 3305, Taiwan.
authors.forename: Nan-Kai
authors.initials: NK
authors.lastname: Wang
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D001284:Atrophy; D005260:Female; D006801:Humans; D007223:Infant; D058449:Intravitreal Injections; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects*; D012160:Retina / Q000187:drug effects / Q000473:pathology; D058499:Retinal Dystrophies / Q000139:chemically induced* / Q000175:diagnosis; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012175:Retinoblastoma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan
keywords: Intravitreal injection; Melphalan; Retina; Retinoblastoma; Toxicity