Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review

Br J Ophthalmol. 2014 Mar;98(3):292-7. doi: 10.1136/bjophthalmol-2013-303885. Epub 2013 Nov 1.


Purpose: To describe the ocular side effects in patients receiving intravitreal injection therapy (IViT) for retinoblastoma.

Methods: PubMed (1946-present), Scopus (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index-Science (1990-present) electronic databases were searched to identify all published reports of therapeutic intravitreal injections for retinoblastoma in humans.

Results: Ten studies with original IViT ocular side effect data were included in this systematic review. In these combined reports, a total of 1287 intravitreal injections were given to 306 eyes of 295 patients, with a mean follow-up of 74.1 months. Two hundred sixty-one (88.5%) patients received comparatively standard melphalan IViT doses (8-30 mcg). Ocular side effects occurred in 38 patients (17 significant, 21 minor). The proportion of patients experiencing potentially significant ocular side effects following standard melphalan IViT regimens was 0.031 (8/261; 95% CI 0.013 to 0.06). The side effects of these eight included iris atrophy in three, two each with chorioretinal atrophy and vitreous haemorrhage and one with retinal detachment. Of the other nine patients with significant complications, five experienced sight-threatening complications following dramatic dose escalations (four with melphalan, one with thiotepa), three experienced complications that are commonly associated with concurrent therapies given to these patients and one had a retinal detachment. Of the 61 patients receiving IViT via safety-enhancing injection techniques, all six significant side effects were either attributed to the therapeutic dose or confounded by concurrent treatments.

Conclusions: Significant ocular complications following IViT for retinoblastoma are uncommon, and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. Care must be taken in the dosing of intravitreal treatments to avoid potentially irreversible vision loss.

Keywords: Child Health (Paediatrics); Neoplasia; Retina; Vitreous.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Atrophy / chemically induced
  • Corneal Dystrophies, Hereditary / chemically induced
  • Humans
  • Intravitreal Injections
  • Iris / pathology
  • Melphalan / administration & dosage
  • Melphalan / adverse effects*
  • Retinal Detachment / chemically induced
  • Retinal Neoplasms / drug therapy*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / pathology
  • Vitreous Hemorrhage / chemically induced


  • Antineoplastic Agents, Alkylating
  • Melphalan

Supplementary concepts

  • Chorioretinal atrophy, progressive bifocal