Is intravitreal topotecan toxic to retinal function?

Br J Ophthalmol. 2021 Jul;105(7):1016-1018. doi: 10.1136/bjophthalmol-2020-316588. Epub 2020 Jul 14.

Abstract

Background: Intravitreal injections of topotecan are used in the management of retinoblastoma with vitreous seeds. This study evaluated whether intravitreal topotecan was associated with retinal toxicity.

Methods: Retrospective cohort study of patients with retinoblastoma who were treated with intravitreal topotecan at Memorial Sloan Kettering Cancer Center between December 2014 and May 2019. Electroretinogram (ERG) responses under anaesthesia were measured immediately before treatment with intravitreal topotecan and at the next visitor approximately one-month. Ocular toxicity was defined by a decrease in the ERG response at 30 Hz at follow-up.

Results: Ocular toxicity was evaluated by ERG on 50 evaluable injections administered to 28 eyes. 22 (44.0%) injections were performed with concurrent intravitreal melphalan. The median time to ERG measurement following an injection was 27 days. By using a paired t-test, intravitreal topotecan combined with melphalan (n=22) at a dose of 25 μg or 30 μg was associated with a significant decrease in ERG amplitude at follow-up (p=0.046, 95% CI -20.4 μV to -0.2 μV). Among eyes that only received topotecan (n=28) at doses of 20 μg or 30 μg, there was not a significant difference in ERG amplitude measured (p=0.85, 95% CI -7.0 μV to 5.8 μV).

Conclusion: Intravitreal topotecan combined with intravitreal melphalan was associated with a decrease in ERG amplitude; there was not a significant decrease in ERG amplitude observed in patients who received topotecan alone. These findings suggest that intravitreal topotecan injections at doses of 20 μg or 30 μg are not associated with retinal toxicity in patients with retinoblastoma.

Keywords: Electrophysiology; Neoplasia; Pharmacology; Retina; Treatment Medical.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols
  • Electroretinography / drug effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Intravitreal Injections
  • Male
  • Melphalan / administration & dosage
  • Retina / drug effects*
  • Retinal Neoplasms / drug therapy*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / pathology
  • Retrospective Studies
  • Topoisomerase I Inhibitors / administration & dosage
  • Topoisomerase I Inhibitors / toxicity*
  • Topotecan / administration & dosage
  • Topotecan / toxicity*

Substances

  • Antineoplastic Agents, Alkylating
  • Topoisomerase I Inhibitors
  • Topotecan
  • Melphalan