Use of Membrane Blue in ILM and ERM Peeling

A retinal surgeon shares his experience with this new visualization agent.

BRIAN C. JOONDEPH, MD, FACS

Retinal surgeons are familiar with the membrane staining technique commonly used to facilitate the identification and removal of epiretinal membranes and the internal limiting membrane.

However, only recently has there been an FDA-approved product specifically for this purpose: Membrane Blue 0.15% (a brand of trypan blue dye) from Dutch Ophthalmic USA (Exeter, NH). Other products, such as indocynanine green and triamcinolone acetonide, can be used off-label for membrane staining and identification

The purpose of this article is to review some practical tips to maximize the benefits of Membrane Blue during vitrectomy surgery. These tips are based on anecdotal observations resulting from my use of Membrane Blue since 2001.

USES OF MEMBRANE BLUE

Membrane Blue stains epiretinal membranes (ERMs) better than internal limiting membrane (ILM). The reason for this is that trypan blue is not absorbed by living cells with intact cell membranes, but it does cross cell membranes of dead cells. ERM is dead tissue — hence the robust staining of ERM compared to ILM, which is living tissue and thus does not absorb trypan blue.

I use Membrane Blue as a surgical adjunct in removal of all but the most prominent ERMs. Incomplete ERM peeling, leaving small remnants of ERM behind, may account for the approximately 10% rate of ERM recurrence after surgical removal. Being able to visualize all of the ERM tissue increases the chance of complete removal. Often edge identification or creation can be difficult in milder ERMs. The blue staining of the ERM makes this process much easier and safer.

Some ERMs are subtle and difficult to visualize, yet they may be clearly seen on optical coherence tomography scanning and may be symptomatic in select patients. Intraoperatively, the ERM may be difficult to visualize and it may not be possible to identify an edge. This can lead to incomplete peeling or, in some cases, no peeling, if the ERM cannot be identified. Inability to remove the ERM or excessive retinal trauma are undesirable in a patient with a symptomatic 20/30 ERM. Staining with Membrane Blue solves this problem, allowing safe and complete ERM removal (Figure 1).

Figure 1. Partially peeled epiretinal membrane stained with Membrane Blue.

Eyes with proliferative vitreoretinopathy often have surface ERMs that may not be visible, especially on the surface of detached retina. Staining with Membrane Blue makes these peripheral ERMs and starfolds clearly visible and amenable to removal (Figure 2). The more complete the ERM removal, the greater the chance of long-term retinal reattachment in proliferative vitreoretinopathy surgery.

Figure 2. Stained epiretinal membrane at the apex of a retinal starfold grasped with intraocular forceps.

The ILM can be stained with Membrane Blue, although the quality of staining is variable, sometimes very faint and at other times quite prominent (Figure 3). With concerns about indocynanine green toxicity, Membrane Blue may be a safer option in macular hole cases. Later in this article, I will discuss several techniques to increase the quality of ILM staining.

Figure 3. Partially peeled internal limiting membrane stained with Membrane Blue in a case of macular hole.

Finally, Membrane Blue is helpful during vitrectomy for floaters or vitreomacular traction, by staining the vitreous and allowing clear visualization of the posterior hyaloid (Figure 4). In patients with floaters, leaving even a moderate amount of vitreous behind may leave the patient dissatisfied with their residual floaters. Using Membrane Blue staining of the vitreous confirms that a vitreous detachment is present and that only the far peripheral vitreous is left in place. In cases of vitreomacular traction, there can be schisis cavities in the vitreous cavity. It may be easy for the surgeon to feel that the vitrectomy is complete, while only removing a portion of the vitreous schisis cavity. Membrane Blue staining reveals the remaining vitreous. In diabetic vitrectomy, it is of utmost importance to remove the posterior hyaloid. Again, staining and identification of residual hyaloid with removal will provide better long-term outcomes in diabetic vitrectomy.

Figure 4. Membrane Blue stained posterior hyaloid grasped and elevated with the vitrectomy cutter.

SIMILARITIES AND DIFFERENCES WITH OTHER DYES

Let's compare Membrane Blue to two other commonly used membrane stains: indocynanine green and triamcinolone acetonide. Indocyanine green, by nature of its property of binding to plasma proteins, provides more robust staining of ILM, which is living tissue. Indocyanine green will also stain the vitreous. There are reports in the literature about potential indocyanine green toxicity to the retina and/or retinal pigment epithelium, both in vivo and in vitro, as well as lower visual acuity results in macular hole surgery when indocyanine green is used.

Triamcinolone does not actually stain tissue like indocyanine green or Membrane Blue, but adheres to vitreous providing clear identification of cortical vitreous. While it does not stain ERM or ILM, it settles on the surface of these membranes, providing a clear delineation of where peeling has taken place. It will not, however, show residual or missed membranes that would be stained by either indocyanine green or Membrane Blue. Triamcinolone has minimal if any toxicity issues, other than a potential intraocular pressure rise in steroid responders.

ADMINISTRATION OF MEMBRANE BLUE

Membrane Blue comes in a pre-filled syringe. It can be injected with either a soft-tip cannula or long needle, size determined by the gauge size of surgery. Upon injection, Membrane Blue disperses in the vitreous cavity. The dark blue color blocks out the red reflex and suddenly visualization within the vitreous cavity is nil. To avoid dispersion it is preferable for the Membrane Blue to settle only over the macula. There are several ways to do this.

Membrane Blue can be injected under air. First, perform a near complete fluid-air exchange, and then inject the Membrane Blue. It will puddle over the macula, providing a more intense stain, and avoid the dispersion (Figure 5). After a minute, most of the dye can be aspirated with an extrusion cannula before resuming fluid infusion. The residual dye at this point won't impair visualization. This also avoids the dye coming into contact with the intraocular lens, in pseudo phakic eyes. Hydrophilic intraocular lenses can potentially be tinted blue through contact with trypan blue dye.

Figure 5. Membrane Blue injected under air, pooling over the posterior pole.

Another technique is to chill the Membrane Blue by keeping the package in the refrigerator before use. The heavier specific gravity of the cold dye will cause it to slowly sink and settle over the macula. The fluid infusion should be turned off during Membrane Blue injection to avoid dispersion. Then slowly aspirate most of the dye from the macula before resuming fluid infusion, again to avoid dispersion.

A third option is to dilute the Membrane Blue with a small amount of 50% dextrose. The Membrane Blue will then have a higher specific gravity, sinking over the macula much like chilled Membrane Blue.

Staining under air is particularly useful when ILM staining is desired, as the normal ILM staining under fluid may be faint. Care should be taken in eyes with silicone intraocular lenses as lens condensation may temporarily affect visualization during the air phase, affecting removal of the dye puddle over the macula. If the dye disperses and visualization disappears in a “blue-out” waiting for a minute with infusion flowing will wash out most of the excess dye through the sclerotomies or ports.

As an aid to vitreous staining, the opposite approach is desired, with dye dispersal being the goal, ensuring good staining of the vitreous. Injecting Membrane Blue into the mid-vitreous cavity with infusion flowing will disperse the dye throughout the vitreous cavity.

Reinjection of Membrane Blue can be useful, especially in ILM peeling cases. ILM staining tends to be transient. By the time an ILM edge is created, much of the staining may have worn off. Injecting a small amount of dye, especially near the created edge, allows staining of both sides of the ILM flap, providing good visualization for subsequent peeling. Reinjection of Membrane Blue in ERM cases is advised, particularly in cases in which the ERM is removed in multiple sections, rather than a single prominent sheet. Restaining provides confirmation that all of the ERM has been removed, without leaving any remnants behind.

In proliferative vitreoretinopathy cases, injecting in a fluid-filled eye is preferable. The membranes can then be peeled under fluid or if the surgeon prefers, perfluoron can be injected, the ERMs will be visible through the perfluoron and can be readily identified and removed (Figure 6).

Figure 6. Stained ERM being peeled under perfluoron.

As Membrane Blue is a new product, make sure your surgical staff is aware of the difference between Vision Blue and Membrane Blue. Both are trypan blue dye, in concentrations of 0.06% and 0.15%, respectively. While Vision Blue is excellent for lens capsule staining during cataract surgery, being 2.5 times weaker than Membrane Blue makes Vision Blue inadequate for retinal membrane staining. As Membrane Blue has only recently been approved and made available, Vision Blue has been available for many years and many of us have tried using it as a membrane stain, but without success. This has resulted in many jaded opinions against trypan blue staining, but the two different concentrations are quite different in terms of staining quality.

CONCLUSION

In conclusion, Membrane Blue is a welcome addition to the surgical adjuncts we have at our disposal to improve our surgical efficiency and outcomes. Its greatest use is in staining of epiretinal membranes both in macular pucker cases and complex retinal detachments with proliferative vitreoretinopathy. Retinal surgeons should try it and add it to their surgical “bag of tricks.” RP