Involvement of Illumination in Indocyanine Green Toxicity After Its Washout in the Ex Vivo Rat Retina

Abstract

Purpose To elucidate the involvement of illumination in indocyanine green (ICG) retinal toxicity. Methods We incubated isolated rat retinas with or without illumination after exposure to 0.5 % ICG. We also examined whether a time lag following ICG exposure prior to illumination altered the damage. Toxicity was evaluated by histological and biochemical assays, including measurement of lactate dehydrogenase (LDH) release. Results Retinas fixed immediately after ICG exposure showed minimal morphological changes. However, illumination for 3 h at 34 °C starting after washout of ICG selectively damaged the outer nuclear layer. Retinas incubated for 3 h under the same condition in the dark showed preserved morphology but were damaged by subsequent illumination. When retinas were illuminated after washout of ICG at a lower temperature (30 °C), the damage was attenuated. Results obtained using LDH release were consistent with these morphological changes. Conclusions Incubating retinas in the dark and cooling after ICG exposure significantly inhibited retinal damage, suggesting that ICG interacts with illumination to induce retinal damage. Summary Statement Illumination after indocyanine green (ICG) exposure damaged the outer nuclear layer in isolated rat retinas. Incubating retinas in the dark or cooling after its exposure attenuated the damage, indicating phototoxic properties of ICG. Phototoxic damage developing after ICG exposure suggests the importance of protecting the retina from light during and after vitrectomy.

Phototoxicity of Indocyanine Green and Brilliant Blue G under Continuous Fluorescent Illumination on Cultured Human Retinal Pigment Epithelial Cells

“…3,10,11 Although ICG is used widely as a vital dye in ILM peeling without causing surgical complications, its dose-and exposure time-dependent cytotoxicity as well as phototoxicity have been reported in experimental studies. [12][13][14][15][16][17][18][19][20] Moreover, a metaanalysis indicates that treatment of macular hole with ICG results in worse functional outcomes than treatment without ICG. [21][22][23] Thus, intravitreal ICG injection remains controversial.…”

“…37 However, phenol red and FBS in the medium absorb visual light. Kernt et al 12 and Tokuda et al 20 reported phototoxicity of ICG under conditions simulating irradiation by surgical light during intraocular surgery. Instead of culture medium, Kernt et al used PBS in which they maintained the cells during light irradiation for a duration of 10 minutes or shorter.…”

A Review of Indocyanine Green Fluorescent Imaging in Surgery

“…The decomposition products thermally decompose further to several carbonyl compounds. However, according to a recent study by Tokuda et al, ICG seems to be somewhat phototoxic for the retina [ 40 ].…”

Ultrastructure of the Membrana Limitans Interna after Dye-Assisted Membrane Peeling

“…Unfortunately, the preferable biomechanical properties of ICG are inextricably linked to its photolysis that generates cytotoxic metabolites [33]. Future generations of staining substances should ideally cover both aspects to dispel current skepticism of dye-assisted macular surgery.…”