Toxicity of indocyanine green injected into the subretinal space: subretinal toxicity of indocyanine green

Retina. 2003 Oct;23(5):675-81. doi: 10.1097/00006982-200310000-00012.


Purpose: To evaluate the toxicity of indocyanine green (ICG) injected into the subretinal space. Indocyanine green may come in contact with photoreceptors and retinal pigment epithelium through a macular hole during ICG-assisted peeling of the internal limiting membrane.

Methods: Balanced salt solution or ICG of various concentrations (0.6, 1.25, 2.5, or 5.0 mg/mL) was injected into the subretinal space of rabbit eyes and removed after 1 minute. After 3 days, 1 week, and 4 weeks, the eyes were enucleated and evaluated by light microscopy and electron microscopy.

Results: When the ICG of 1.25 mg/mL or higher concentration was injected into the subretinal space, degenerative changes of the photoreceptors and the retinal pigment epithelial cells were found after 3 days with light and electron microscopy. After 1 week, the outer retina was disintegrated and the photoreceptors were not found. After 4 weeks in the eyes with 1.25 mg/mL ICG, short photoreceptors and a thin outer nuclear layer were seen. In the eyes with 2.5 mg/mL or higher ICG, the photoreceptors and the outer nuclear layer were destroyed completely.

Conclusion: The results of this study suggest that the ICG of 1.25 mg/mL or higher concentration has toxicity to the outer retina of the rabbit and may cause adverse effects on the functional outcome after macular hole surgery.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Coloring Agents / administration & dosage
  • Coloring Agents / toxicity*
  • Dose-Response Relationship, Drug
  • Indocyanine Green / administration & dosage
  • Indocyanine Green / toxicity*
  • Injections
  • Ophthalmoscopy
  • Photoreceptor Cells / drug effects
  • Photoreceptor Cells / ultrastructure
  • Pigment Epithelium of Eye / drug effects
  • Pigment Epithelium of Eye / ultrastructure
  • Rabbits
  • Retina / drug effects*
  • Retina / ultrastructure


  • Coloring Agents
  • Indocyanine Green