Vital staining with indocyanine green: a review of the clinical and experimental studies relating to safety

Abstract

Indocyanine green (ICG) is extremely effective when used as a vital stain during macular hole surgery. By staining the internal limiting membrane, ICG facilitates removal of this delicate and sometimes hard to visualize structure. There is, however, considerable debate regarding its safety. This review considers the clinical and experimental studies of ICG and a related agent, infracyanine green. Some clinical papers show visual field defects, reduced visual acuity, and persistence of ICG at the macula and optic nerve. Other clinical studies fail to demonstrate toxicity. The experimental studies are also conflicting, but there are emerging trends. These suggest that surgeons who continue to use ICG should use concentrations not greater than 0.05 mg/ml, in fluid-filled eyes, with short exposure times, iso-osmolar solutions, and avoid proximal or prolonged endoillumination of stained tissue. A smaller number of studies suggest that infracyanine green produces similar staining to ICG, and may possibly be safer, but there are too few well-designed studies to reach a conclusion. Although the use of ICG continues, on the balance of evidence, this review suggests that it is has the potential to produce subtle visual damage.

Predicting Visual Outcome following Surgery for Idiopathic Macular Holes

“…Indocyanine green (ICG) is a fluorescent dye that formerly gained widespread use to visualise the ILM. However, there were concerns regarding the safety of ICG use [21], and recent meta-analyses of ILM peeling in MH surgery showed that visual outcomes were significantly worse in the group with ICG application [22,23]. Trypan blue and triamcinolone acetonide have been used to replace ICG [24,25,26,27], but there are reports suggesting retinal toxic effects associated with these agents [28,29,30].…”

Biochemical Analysis and Decomposition Products of Indocyanine Green in Relation to Solvents, Dye Concentrations and Laser Exposure

“…Such a difference may explain why several clinical investigations have shown little or no retinal toxicity with IfCG application [20,21,22]. Iodine and its derivates may be toxic to the RPE.…”

Pars Plana Vitrectomy for Diabetic Macular Edema

“…Articles using intravitreal vital stains to assist with peeling of the internal limiting membrane (ILM) were not excluded. [33][34][35][36] Similar eligibility criteria were applied to the safety analysis, except that studies did not need to be RCTs or have a control group, the minimum VA follow up did not apply, and they need not report CRT. Prospective, retrospective, controlled and uncontrolled studies, including case reports, were eligible for the safety analysis.…”