Indocyanine green accused.

T he concept of retinal vital staining is not new. There has however been renewed interest in the subject since indocyanine green (ICG) was introduced as a vital stain to highlight the internal limiting membrane (ILM) during macular surgery. ICG’s well known role in cardiac and choroidal angiography exploits its properties as a fluorophore, but its role as a macular vital stain relies on its properties as a chromophore or biological stain. Biological stains such as ICG have specific atomic groupings that impart colour (C=S, C=N, N=N, N=O, and NO2). ICG is therefore able to stain the thin, optically clear ILM, assisting maculorhexis in much the same way that trypan blue assists capsulorhexis. ICG has more recently been used to help remove epiretinal membranes. Initial reports were favourable. Subsequently, some of the most prominent exponents of ICG reported possible toxicity, and enthusiasm waned. More recently there have again been papers showing a favourable outcome, 10 and the debate continues. The article by Hillenkamp et al in this issue of the BJO (p 437) supports the continued use of ICG, but it should not be read in isolation. This editorial presents the case for and against ICG macular vital staining, considering the clinical and experimental evidence in turn. Hillenkamp’s study suggests that ICG vital staining is both safe and effective. It reports a retrospective analysis of two consecutive series of patients undergoing removal of epiretinal membranes, with and without the aid of ICG. The strength of this study lies in its detailed analysis of visual function. Outcome measures included subjective improvement, Amsler grid, corrected visual acuity (VA), slit lamp biomicroscopy, 10 and 30 degree automated perimetry, Goldmann kinetic perimetry, and optical coherence tomography. The results of surgery with and without ICG were broadly similar, except that the ICG group had significantly fewer residual or recurrent epiretinal membranes. As noted by the authors, this may be because of longer follow up in the ‘‘no ICG’’ group, but it is distinctly possible that ICG enhanced membrane removal. Importantly, this study suggests that visual outcome was not compromised by ICG. This finding agrees with several reports showing good outcome following macular hole surgery with ICG assisted ILM removal. The clinical argument in support of ICG rests not only on reports of good outcome, but also on the deficiencies of the patient studies showing toxicity. Many employed staining routines that are not now thought to be ideal. Some used contact times of several minutes, and solutions of up to 5 mg/ml (0.5%), yet approximately 1 mg/ml produces adequate staining, and many surgeons now use exposure times of 30 seconds or less. In addition, many investigators dissolved ICG in 0.5 ml of distilled water, before mixing with 4.5 ml of a balanced saline solution (BSS). This produces a 275 mOsm solution that is hypo-osmotic relative to agents such as BSS (302 mOsm). It has been suggested that ICG toxicity is caused, or at least aggravated, by low osmolarity. The experimental reports of ICG toxicity are also imperfect. One of the most influential studies exposed human cadaveric eyes to ICG and illumination with a surgical endolight. The selected histological images were dramatic, with profound disruption of cellular architecture. This is not consistent with clinical observations, as reports of ICG toxicity generally show only mild to moderate deficits. Other authors were not able to repeat these observations in freshly enucleated pig eyes. Further, the validity of using enucleated eyes to model vascularised, viable retina is uncertain.