• Cataract/Anterior Segment

    Internationally, trypan blue has been used as an adjunct for improving visualization of the anterior capsule during phacoemulsification of mature white cataracts for the past few years. The United States ophthalmic community therefore, hailed its approval in 2004 by the Food and Drug Administration (FDA). Over time, ingenuity and observation by astute clinicians and surgeons have generated other uses for the dye, and many distinctive applications have been demonstrated. This article will discuss some of the ways that physicians are currently using trypan blue, the techniques for its application, safety considerations when using the dye, and the issues surrounding the dye’s recall by a compounding pharmacy subsequent to pseudomonal contamination.

    Clinical Applications

    Conditions resulting in a compromised red reflex contribute to poor visualization of the anterior capsule during cataract surgery, making capsulorrhexis far more difficult. A poorly performed anterior capsulorrhexis can lead to increased complications rates. Capsular staining is, therefore, regarded as helpful in eyes containing mature cataract and in eyes with a poor red reflex due to conditions such as corneal scarring and edema, asteroid hyalosis, vitreous hemorrhage, and retinal disease (Cataract Refract Surg Today. 2005;5:3:34-37).

    In corneal surgery, trypan blue can be used to stain the posterior stromal fibers during deep lamellar endothelial keratoplasty (DLEK) and to stain the endothelium in Descemet’s stripping endothelial keratoplasty (DSEK) prior to the removal of Descemet’s membrane. Trypan blue has also proven to be a useful adjunct in vitreoretinal surgery and in cases of proliferative vitreoretinopathy. Dye enhancement has been used to facilitate the identification, delineation, and removal of epiretinal membranes, the internal limiting membrane, and the posterior hyaloid during vitrectomy cases (Retina. 2004;24:736-738). In oculoplastics surgery, an extraocular indication has been described for staining Tenon’s capsule during enucleation surgery (Arch Ophthalmol. 2005;123:1125-1126).

    Application Techniques

    Surgeons have long used dyes like indocyanine green, fluorescein, and trypan blue to stain the anterior capsule in order to facilitate the surgical procedure. However, studies comparing these 3 dyes have concluded that trypan blue provides significantly more intensive staining of the anterior lens capsule than the others (Cataract Refract Surg Today. 2005;5:3:34-37). Trypan blue is easier to use than indocyanine green, because it comes in a premixed solution, and it is available at a more economical price.

    There are 2 widely employed techniques for cataract capsular staining, the first being injection of trypan blue into the anterior chamber under an air bubble and the second being injection under viscoelastic. In both techniques a drop of the capsular dye is placed within the chamber after introducing either filtered air or a viscoelastic material. Both scenarios involve painting the capsule prior to the initiation of a continuous curvilinear capsulorrhexis.

    Wong et al (Eye. 2005; [in press]) conducted a prospective, randomized trial of 52 consecutive, mature white cataracts in order to compare the 2 techniques. In the study, one-half of the eyes were assigned to the air group and the other to the viscoelastic group. There were no statistically significant differences in phacoemulsification time, total operating time, post-operative best-corrected vision, central corneal thickness, or endothelial cell count between the 2 groups. The authors concluded that both methods were equally effective and safe. However, there are certain advantages and disadvantages associated with each method
    (Table 1).

    Table 1. Advantages and disadvantages of anterior capsule staining under an air bubble vs. viscoelastic.

    Anterior Capsule Staining Techniques Advantages Disadvantages
    Under air bubble
    •  Creation of a 'dye lake’ over the lens capsule
    • More economical
    • More difficult to maintain anterior chamber depth
    • Dye more likely to leak out of anterior chamber
    Under viscoelastic
    • Easier to maintain the anterior chamber
    • Minimizes contact of dye with corneal endothelium and potential surgical trauma
    • Requires mechanical spreading of the dye
    • Requires larger volume of viscoelastic and may increase cost of surgery
    • More time-consuming for viscoelastic exchange

    Wong VW, Lai, TY, Lee GK, Lam PT, Lam DS. A prospective study on trypan blue capsule staining under air vs. under viscoelastic. Eye. 2005; [in press].

    The associated instability of the anterior chamber is a concern when staining under an air bubble. Alternatively, physicians have the potential to obscure visibility at the viscoelastic anterior capsule interface when staining under viscoelastic. Surgeons have addressed some of these concerns by creating modifications to these techniques. These include injection of trypan blue mixed with a viscoelastic material and a sandwich injection between viscoelastic and balanced salt solution. Several single step techniques have also been illustrated in the literature.

    One method involves replacing the aqueous humor with trypan blue and then injecting the capsular dye directly into the anterior chamber through a paracentesis portwithout initially introducing air or viscoelastic into the eye (Ophthalmic Surg Lasers Imaging. 2005;36:432-434). Another technique described by Caporossi et al (Ophthalmic Surg Lasers Imaging. 2005;36:432-434) involves injecting a single drop of trypan blue under a dispersive viscoelastic. These techniques are presumably easier, faster, and less problematic than the 2 traditional methods described above.

    Safety Concerns

    Recent studies should allay concerns that trypan blue will negatively affect corneal endothelial cells. Chang et al (J Cataract Refract Surg. 2005;31:792-798) investigated the corneal endothelial cytotoxicity of dyes for capsule staining in cataract surgery. They found no cytotoxic effects in rabbit corneal endothelial cells in culture that were exposed to trypan blue for 1 minute at considerably higher concentrations than needed for surgery.

    Nevertheless, the possibility of bacterial infection after instilling an agent into the eye remains real. C ompounding pharmacy Custom RX issued a nationwide recall in August 2005, following an FDA report that certain batches of trypan blue distributed by the company may have been contaminated with Pseudomonas aeruginosa, leading to vision loss in at least 2 patients. Because patient safety is of utmost importance, physicians intent on using trypan blue at this time should purchase the product in a premixed, sterilized form from Dutch Ophthalmic Research Center’s (DORC) U.S. division, where it is known as VisionBlue (0.06%). VisionBlue is sold as a sterile, premixed solution in a 0.5 ml aliquots per1-ml syringe at $40 per vial. One box contains 10 syringes.

    Ophthalmologists should also exercise caution when inserting hydrophilic intraocular lenses (IOLs) in cataract patients, because the IOL can absorb trypan blue and become discolored, if the dye is used for prolonged periods of time. Although IOL discoloration and other adverse reactions such as minor staining of the posterior capsule and vitreous have generally been self-limited and of short duration, typically resolving within 1 week, the FDA does not recommend using the dye at all in conjunction with hydrophilic IOL implantation. Teratogenic effects have also been noted in early animal research when trypan blue is injected intravenously at high doses.

    Conclusion

    Staining the anterior capsule is a helpful and simple procedure when poor red reflex is a concern during phacoemulsification. Trypan blue is an effective stain that is useful in many other instances beyond routine staining of the anterior capsule during cataract surgery. Different techniques for applying this stain have been described without significant differences in surgical outcomes. Because of the explosion of possible uses for this drug, it is likely that more clinician initiated modifications for this dye will emerge in the future. A relatively uncultivated niche exists for improving technique in the formative years of surgical training. Enhanced visualization can also promote the junior surgeon’s ability to evaluate clinical structural relationships even in the most routine cases and may result in fewer complications as one learns the critical steps of phacoemulsification surgery.

    References

    1. Chang DF. Trypan blue versus indocyanine green: a clinical comparison of these dyes for capsular staining. Cataract Refract Surg Today. 2005; 5:3:34-37.
    2. Vote BJ, Russell MK, Joondeph BC. Trypan blue assisted vitrectomy. Retina. 2004;24:736-738.
    3. Cheung LM, Wilcsek GA, Francis IC, Coroneo MT. Staining of the tenon capsule with trypan blue during enucleation surgery. Arch Ophthalmol. 2005;123:1125-1126.
    4. Wong VW, Lai, TY, Lee GK, Lam PT, Lam DS.A prospective study on trypan blue capsule staining under air vs under viscoelastic. Eye. 2005; [in press].
    5. Chang YS, Tseng SY, Tseng SH, Chen YT, Hsiao JH. Comparison of dyes for cataract surgery. Part 1: cytotoxicity to corneal endothelial cells in a rabbit model. J Cataract Refract Surg. 2005; 31:792-798.
    6. Caporossi A, Balestrazzi A, Alegente M, Casprini F, Caporossi T. Trypan blue staining of the anterior capsule: the one-drop technique. Ophthalmic Surg Lasers Imaging. 2005; 36:432-434.

    Author Disclosure

    The authors state that they have no financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service. Dr. Afshari, however, has received a Career Development Award from the organization Research to Prevent Blindness.