To the Editor:—  Indocyanine green (ICG) has been identified as a potential alternative to epinephrine as a means of detecting inadvertent intravascular injection of local anesthetic during epidural anesthesia. Dietz and Jaffe 1have shown apparent neurotoxicity with this agent and cautioned against its use. They noted that neurotoxicity had not been reported previously. However, there are a series of reports of possible retinal neurotoxicity that may support the authors’ claim. ICG is commonly used as an intraoperative vital stain to identify and remove the internal limiting membrane during macular surgery. 2Concerns have been expressed regarding its safety. 3Some experimental reports have shown ICG mediated neororetinal 4and retinal pigment epithelial cell damage. 5There are also clinical studies showing functional visual loss after ICG-assisted macular surgery. 6ICG is usually mixed in distilled water and then saline, resulting in a hypoosmolar solution. Some reports suggest that it is the combined exposure to low osmolarity and ICG that produces cell damage. 7Authors have suggested alternative means of preparing ICG, and other agents, such as infracyanine green and trypan blue, have been advocated. 8Other vital stains, such as sodium fluorescein, are widely available and well tested. Many of these and other related articles may be of interest to readers concerned about the safety of ICG.

The Rayne Institute, St. Thomas’ Hospital, London, United Kingdom.

Dietz FB, Jaffe RA: Indocyanine green: Evidence of neurotoxicity in spinal root axons. Anesthesiology 2003; 98:516–20
Burk SE, Da-Mata AP, Snyder ME, Rosa R-HJ, Foster RE: Indocyanine green-assisted peeling of the retinal internal limiting membrane. Ophthalmology 2000; 107:2010–4
Kampik A, Sternberg P: Indocyanine green in vitreomacular surgery (why) is it a problem? Am J Ophthalmol 2003; 136:527–9
Gandorfer A, Haritoglou C, Gandorfer A, Kampik A: Retinal damage from indocyanine green in experimental macular surgery. Invest Ophthalmol Vis Sci 2003; 44:316–23
Sippy BD, Engelbrecht NE, Hubbard GB, Moriarty SE, Jiang S, Aaberg TM Jr, Aaberg Sr TM, Grossniklaus HE, Sternberg P Jr: Indocyanine green effect on cultured human epithelial cells: Implications for macular hole surgery. Am J Ophthalmol 2001; 132:433–5
Haritoglou C, Gandorfer A, Gass CA, Schaumberger M, Ulbig MW, Kampik A: The effect of indocyanine-green on functional outcome of macular pucker surgery. Am J Ophthalmol 2003; 135:328–37
Stalmans P, Van Aken EH, Veckeneer M, Feron EJ, Stalmans I: Toxic effect of indocyanine green on retinal pigment epithelium related to osmotic effects of the solvent. Am J Ophthalmol 2002; 134:282–5
Stalmans P, Feron EJ, Parys-Van Ginderdeuren R, Van Lommel A, Melles GR, Veckeneer M: Double vital staining using trypan blue and infracyanine green in macular pucker surgery. Br J Ophthalmol 2003; 87:713–6