Effects of indocyanine green injection on the retinal surface and into the subretinal space in rabbits

Retina. 2004 Feb;24(1):80-91. doi: 10.1097/00006982-200402000-00012.


Purpose: To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the subretinal space of rabbit eyes.

Methods: Twenty-two Dutch-belted rabbits underwent two-port vitrectomy followed by injection of ICG (5 mg/mL) on the retinal surface and into the subretinal space. Balanced salt solution (BSS) was also injected subretinally. The locations where ICG was delivered (both epiretinal and subretinal) were exposed to light from an endoilluminator for 7 minutes. The animals were examined at 1, 7, and 14 days after surgery. The eyes were studied by fluorescein angiography as well as light and electron microscopy.

Results: No damage was observed after epiretinal ICG injection, but subretinal ICG injection resulted in damage to the outer nuclear layer, photoreceptor inner and outer segments, and retinal pigment epithelium. This damage was more severe with longer follow-up. Control experiments without ICG, in which balanced salt solution was injected into the subretinal space or light was delivered on the epiretinal surface, demonstrated only damage to the photoreceptor outer segments.

Conclusion: Subretinal delivery of ICG (5 mg/mL) in rabbits induces retinal pigment epithelium, photoreceptor inner and outer segment, and outer nuclear layer damage. These mechanisms of damage may explain the retinal pigment epithelium changes that are sometimes seen after ICG-assisted internal limiting membrane peeling in humans.

MeSH terms

  • Animals
  • Coloring Agents / toxicity*
  • Extracellular Space / drug effects*
  • Fluorescein Angiography
  • Indocyanine Green / toxicity*
  • Injections
  • Neuroglia / drug effects
  • Neuroglia / ultrastructure
  • Photoreceptor Cells, Vertebrate / drug effects
  • Photoreceptor Cells, Vertebrate / ultrastructure
  • Pigment Epithelium of Eye / drug effects
  • Pigment Epithelium of Eye / ultrastructure
  • Rabbits
  • Retina / drug effects*
  • Retina / ultrastructure
  • Vitrectomy


  • Coloring Agents
  • Indocyanine Green