The Role of ICG
In Macular Hole Surgery
When an ILM peel is necessary, ICG offers better visibility but must be used with caution.
By Judy E. Kim, MD
Regarding macular hole surgery, most surgeons agree that:
1. Macular hole surgery is highly successful and beneficial.
2. Posterior hyaloid detachment is essential.
3. When visible epiretinal membranes are present, they should be peeled.
However, some controversies remain on how to improve our anatomic and functional results. I'll address two questions that often arise: Is internal limiting membrane (ILM) peeling beneficial? Is indocyanine green (ICG) needed?
TO PEEL OR NOT TO PEEL ILM?
A number of studies have shown the benefits and drawbacks of ILM peeling. Brooks1 compared ILM peeling versus not peeling the membrane in 160 eyes. He reported a hole closure rate of 100% and vision improvement of two lines or more in 95% of 116 eyes that had ILM peeling. Among 44 eyes without ILM peeling, these rates were 82% and 57%, respectively. He concluded that ILM peeling improves anatomic and visual success in all stages of macular hole, including reopened and failed holes.
On the other hand, research by Margherio and colleagues2 showed no beneficial or adverse effects with ILM peeling in terms of hole closure rate or visual improvement. They concluded that ILM peeling is not essential.
Mester and Kuhn3 did a meta-analysis of all papers published on macular hole surgery through the year 2000. They divided the results into:
1. No peeling
2. Peeling with use of adjuvants, such as platelets
3. Peeling without use of adjuvants.
Although we cannot draw definite conclusions about the benefits of ILM peeling for all types and stages of macular holes, use of ICG staining of ILM may result in more complete peeling in a shorter duration.
They found a higher rate of anatomic success and better visual outcomes in the ILM peeling-only group.
Some studies have shown that a high rate of hole closure was possible when ILM peeling was performed, even with a shorter duration of postoperative positioning. Most of us will consider ILM peeling beneficial for certain types of holes, including chronic holes, failed holes or reopened holes. Many are peeling ILM in stage 3 and stage 4 holes.
Essentially, without a randomized, controlled clinical trial, we cannot draw a definite conclusion about the benefits of ILM peeling for all types and stages of macular holes. How-ever, we can agree that aggressive peeling is not prudent if peeling is difficult to do. This difficulty often arises because we cannot visualize the ILM well, which brings us to a discussion of ICG staining.
TO USE OR NOT TO USE ICG?
The benefit of using ICG in ILM peeling is that it im-proves visualization of the ILM. If you can see it better, you can treat it better. ICG staining of the ILM helps ensure a more complete ILM peeling and may result in less traumatic peeling in a shorter duration.
However, when using ICG intraocularly, we must be concerned about its potential toxicity. I believe the primary influence on toxicity is the concentration of ICG dye. Osmolarity, pH, the time of tissue contact, mechanical factors and in-creased light absorption from ICG may play roles, as well.
Regarding the osmolarity factor, most people dilute the 25-mg vial of ICG with 5 mL of the aqueous solvent that comes with it to yield the 5 mg/mL (0.5%) concentration, which is used in most published data. However, a study by Stalmans and colleagues4 shows that this dilution method is actually hypo-osmotic and can result in significant in vitro cell death after just 5 minutes of exposure. This suggests that we may want to make the solution as iso-osmotic as possible, using less aqueous solvent to dissolve and more BSS to dilute. However, if we limit the volume of ICG injected into the eye, this may not play a significant role.
When to Consider ILM Peeling
When Using ICG in ILM Peeling, Use:
When using ICG to stain the ILM, you should use the lowest possible concentration that still allows visualization of the ILM. In a recent study, Gale and colleagues5 found that trypan blue was not toxic to the retinal pigment epithelium (RPE) cultures at study concentrations, but ICG dye demonstrated dose-dependent and exposure-dependent toxicity. A clinically useful concentration of 0.5 mg/mL (0.05%) for 1 minute appeared to be safe.
HOW TO USE ICG
In terms of ICG usage for ILM peeling, smaller is better. Less is more. I aim for the lowest concentration, shortest duration, smallest amount and least light exposure. I make the solution as iso-osmotic as possible.
In my ICG recipe, I aim for 0.05% to 0.1% concentration. These lower concentrations give very faint staining when compared to conventional 0.5% concentration. However, once an edge of the stained ILM is elevated and rolled up, the green color intensifies and allows clear visualization of peeled and unpeeled areas.
Before injecting ICG, I turn off the infusion and inject as little as possible (usually 0.2 mL or less) to get the staining. I aim close to the posterior pole but not at the macular hole. Since the staining is instantaneous, I wait 1 minute or less, mostly to let some more of the ICG in the vitreous to settle down.
Finally, I turn on the infusion and aspirate as much of the ICG as possible. If you suspect a retinal tear in the posterior pole, I suggest that you do not use ICG, since subretinal migration of ICG has been shown to be toxic to the RPE.
ICG IN PRACTICE
ILM peeling has improved the success of macular hole surgery for certain types of macular holes. When peeling ILM, you will find ICG staining offers better visibility to determine the extent of the peel. However, you should use it with caution. Other agents, such as trypan blue, may be safer and will need to be studied further to offer our patients improved surgical outcomes.
Dr. Kim is an associate professor of ophthalmology at the Medical College of Wisconsin in Milwaukee.
1. Brooks HL Jr. Macular hole surgery with and without internal limiting membrane peeling. Ophthalmol. 2000;107:1939-1948.
2. Margherio RR, Margherio AR, Williams GA, et al. Effect of perifoveal tissue dissection in the management of acute idiopathic full-thickness macular holes. Arch Ophthalmol. 2000;118:495-498.
3. Mester V, Kuhn F. Internal limiting membrane removal in the management of full-thickness macular holes. Am J Ophthalmol. 2000;129:769-777.
4. Stalmans P, Van Aken EH, Veckeneer M, et al. Toxic effect of indocyanine green on retinal pigment epithelium related to osmotic effects of the solvent. Am J Ophthalmol. 2002;134:282-285.
5. Gale JS, Proulx AA, Gonder JR, et al. Comparison of the in vitro toxicity of indocyanine green to that of trypan blue in human retinal pigment epithelium cell cultures. Am J Ophthalmol. 2004;138:64-69.