Capsular Dye

David F. Chang, MD

Introduction

Dye staining of the anterior capsule is one of the most important advances in the management of complicated cataracts. With the recent U.S. Food and Drug Administration approval of trypan blue, U.S. surgeons are able to fully capitalize on this strategy (Slide 1A and Slide 1B). More than 5 years of worldwide experience demonstrated that capsular staining is safe and effective. Safety, however, depends on the specific dye and the formulation. Lawrence and colleagues¹ reported on four eyes in which intraocular methylene blue, used for capsular staining, resulted in corneal decompensation that eventually required penetrating keratoplasty.

History of Capsule Staining

In 1998, Fritz² published the use of sodium fluorescein dye to stain the anterior capsule for mature cataracts. Because of its small molecular size, fluorescein did not remain confined to the anterior chamber, and the dye diffused into both the lens and the vitreous.

In 1998, Horiguchi and colleagues³ first published the use of 0.5% indocyanine green (ICG) to stain the anterior capsule. They reported a randomized, prospective study of 20 consecutive mature white cataracts, in which one half of the patients received ICG dye and the other half of the patients did not. No statistically significant differences in laser flare-cell photometry, endothelial cell loss or postoperative IOP spikes were noted. Since it is approved for only choroidal angiography, lyophilized ICG (Akorn, Buffalo Grove, Ill.) is sold and packaged with a solvent that, being intended for intravenous (IV) injection, is of an inappropriate pH and osmolality for the anterior chamber. For this reason, Horiguchi mixed the dye using BSS Plus (Alcon, Fort Worth, Texas) and the supplied solvent in a nine parts to one part ratio. The operating room personnel must be careful to either warm or vigorously shake the mixture to fully dissolve the ICG powder. Otherwise, large undissolved particles remain suspended in the solution.

One year later, in 1999, Melles and colleagues⁴ published their use of 0.1% trypan blue dye to stain the anterior capsule in a series of 30 patients with mature cataracts. As with the Horiguchi study, no clinical evidence of increased inflammation, corneal endothelial impairment or elevated IOP was noted; however, no control group existed. After receiving European Conformité Européne (CE) approval, trypan blue 0.06% has been distributed internationally since 1999 by the Dutch Ophthalmic Research Corporation (DORC International, Zuidland, the Netherlands) as VisionBlue. Because it is specifically intended for capsular staining, VisionBlue is packaged in a small vial of solution that is formulated for intraocular use and requires no mixing.

Laboratory and Clinical Studies

ICG and trypan blue were chosen because of laboratory and animal studies supporting their safety. ICG was shown to be nontoxic in rabbits and had been safely used to count cells on human donor keratoplasty buttons.⁵ This was also true of trypan blue, which had been used to examine the endothelium in more than 32,000 donor corneas by the Dutch National Eye Bank.⁴ To gain CE approval in Europe, a standard cytotoxicity study with cultured fibroblasts was used by Melles and colleagues to evaluate four different dyes - trypan blue, indocyanine green, methylene blue and gentian violet. Trypan blue had the best score with the lowest toxicity.⁶

Since these initial reports, both dyes have been adopted for capsular staining worldwide. For example, VisionBlue has been available in 60 countries, with approximately 700,000 units sold by DORC prior to its U.S. release. No published reports of anterior segment complications directly attributable to either dye exist. One prospective randomized, controlled study found no difference in endothelial cell loss when trypan blue was used.⁷ However, concern exists that ICG, when used for internal limiting membrane (ILM) peeling, may be toxic to the retinal photoreceptors and can cause new visual field defects.⁸ A recent study in vitrectomized rabbits found no retinal toxicity from the commercially available 0.06% concentration of trypan blue.⁹ Finally, trypan blue staining of an expandable hydrophilic acrylic IOL has been reported.^10,11 This particular model has the highest water content of the hydrogel class.

The benefit of improved capsule visualization is clinically obvious. However, one randomized study demonstrated that better visualization improves the ability to complete a capsulorrhexis in mature cataracts.⁶ In their paper, presented at the American Academy of Ophthalmology annual meeting in 2001, Dada and colleagues¹² randomized 50 eyes (10 eyes each) to capsular staining with five agents - 0.1% trypan blue, 0.001% gentian violet, 0.5% indocyanine green, 2% fluorescein and autologous hemocoloration. The first three dyes provided superior capsule visualization and capsulorrhexis success rates with no cases of capsule tear extension. Each of the last two groups had poor capsulorrhexis visualization and a 20% extension rate.

In 2000, the author reported one of the first clinical comparisons of ICG and trypan blue for capsular staining.¹³ Trypan blue provides a dark and intense staining of the capsule (Slide 1B). This is particularly helpful when other complicating factors such as corneal edema are present. In addition, trypan blue provides a persistent, long-lasting staining of the anterior capsule (Slide 2). This facilitates nuclear emulsification in mature white and brown lenses, where poor visualization makes it more likely to disrupt the capsulorrhexis with the phaco tip or chopper. For a retrospective study reported at the 2001 American Society of Cataract and Refractive Surgeons annual meeting, the author performed ICG staining in 18 consecutive mature white cataracts between June 1998 and October 1999.¹⁴ Trypan blue was used in 16 consecutive mature lens cases in the United Stated and abroad between November 1999 and November 2000. A planned can opener capsulotomy for extracapsular cataract extraction (ECCE) was performed for one eye in each group. In the eyes undergoing phacoemulsification, a capsulorrhexis was successfully achieved in 15 out of 17 eyes with ICG and in all 15 eyes with trypan blue dye. Both dyes provided excellent capsule visualization and were not associated with complications. Trypan blue staining was more intense and persistent than ICG.

Clinical Indications

In addition to the white cataract, capsular dye should be considered whenever the red reflex is compromised.¹⁵ Examples would include corneal scars or edema, dense anterior cortical spokes, a mature brown nucleus, vitreous hemorrhage and asteroid hyalosis. Trypan blue is especially superior for the brunescent lens, as ICG does not provide enough color contrast with the brown nucleus (Slide 3). The enhanced visualization of a trypan blue-stained capsulorrhexis edge is also helpful in traumatic cataracts to facilitate placement of capsule retractors or capsular tension rings. Other researchers have reported on dye-aided anterior and posterior capsulorrhexis in pediatric cataracts.^16-18

Another underutilized application of capsular dye is teaching phaco techniques.^19,20 Not only can this help a beginning resident to better find and grasp the anterior capsular flap, but it is particularly valuable in learning new phaco techniques, such as phaco flip or phaco chop. With the latter method, highlighting the capsulorrhexis edge with dye helps a transitioning surgeon to avoid overly distending the capsulorrhexis edge with the chopper shaft, or misplacing the horizontal chopper tip peripherally outside the capsular bag (Slide 4A and Slide 4B).

Finally, surgeons sometimes find the capsule flap unexpectedly difficult to visualize when performing the capsulorrhexis. One can stop and perform capsular staining even after the capsulorrhexis has been initiated²¹ because the dye preferentially stains the capsule but not the cortex.²² When irrigating the dye in this situation, do not shallow the chamber, which will tend to extend the tear peripherally.

Staining Techniques

Many surgeons continue to inject the stain beneath an air bubble, as originally described by Horiguchi and Melles (Slide 1A).^3,4 The anterior chamber is filled with air using a 30-gauge cannula through a very small paracentesis. Several drops of dye drawn up into a tuberculin syringe are placed on the anterior capsular surface using the same cannula. While the dye is not toxic to the endothelium, the bubble prevents excessive dilution and helps to confine more dye to the capsular surface. After waiting at least 10 to 15 seconds, the dye is easily irrigated with saline solution before injecting one's ophthalmic visco-device (OVD) of choice. Laureano and Coroneo²³ have suggested omitting the air bubble. Akahoshi²⁴ has described an alternate technique of mixing indocyanine green with viscoelastic. Kayikicioglu and colleagues²⁵ did the same with 0.4% trypan blue. Finally, Marques and colleagues²⁶ have popularized the technique of isolating a puddle of dye on the anterior capsule beneath a partition of cohesive or viscoadaptive (e.g., Healon 5) OVD. This method intensifies the staining compared to the bubble technique where the bubble's meniscus and surface tension displace the dye from the central anterior capsule surface.

Conclusion

Both ICG and trypan blue have been safely and successfully used to enhance visualization of the anterior capsule. Compared to indocyanine green, trypan blue does not require mixing and provides superior and prolonged capsular visualization. Now that it has become the first and only product to receive FDA approval for capsular staining, trypan blue is the author's dye of choice.

References

1. Lawrence MG, Hardten DR, Dvorak JA, Djalilian AR. Methylene blue associated corneal decompensation. Poster presented at: annual meeting of the American Academy of Ophthalmology; November 11-14, 2001; New Orleans, La.
2. Fritz W. Fluorescein blue light-assisted capsulorrhexis for mature or hypermature cataract. J Cataract Refract Surg. 1998;24:19-20.
3. Horiguchi M, Miyake K, Ohta I, Ito Y. Staining of the lens capsule for circular continuous capsulorrhexis in eyes with white cataract. Arch Ophthalmol. 1998;116:535-537.
4. Melles G, de Waard P, Pameyer J, Beekhuis W. Trypan blue capsule staining to visualize the capsulorrhexis in cataract surgery. J Cataract Refract Surg. 1999;25:7-9.
5. McEnerney JK, Peyman GA. Indocyanine green: A new vital stain for use before penetrating keratoplasty. Arch Ophthalmol. 1978;96:1445-1447.
6. Data on file. Dutch Ophthalmic Research Corporation (DORC) International, Zuidland, Netherlands.
7. Van Dooren BT, de Waard PW, Poort-van Nouhuys H, et al. Corneal endothelial cell density after trypan blue capsule staining in cataract surgery. J Cataract Refract Surg. 2002;28:574-575.
8. Kanda S, Uemura A, Yamashita T, et al. Visual field defects after intravitreous administration of indocyanine green in macular hole surgery. Arch Ophthalmol. 2004;122:1447-1451.
9. Veckeneer M, van Overdam K, Monzer J, et. al. Ocular toxicity study of trypan blue injected into the vitreous cavity of rabbit eyes. Graefes Arch Clin Exp Ophthalmol. 2001;239:698-704.
10. Werner L, Apple DJ, Crema AS, et al. Permanent blue discoloration of a hydrogel intraocular lens by intraoperative trypan blue. J Cataract Refract Surg. 2002;28:1279-1286.
11. Bisol T, Rezende RA, Guedes J, Dantas AM. Effect of blue staining of expandable hydrophilic intraocular lenses on contrast sensitivity and glare vision. J Cataract Refract Surg. 2004;30:1732-1735.
12. Dada VK, Sharma N, Pangtey MS, et al. Comparison of various anterior capsular staining methods for capsulorrhexis in white cataracts. Paper presented at: annual meeting of the American Academy of Ophthalmology; November 11-14, 2001; New Orleans, La.
13. Chang DF. Capsule staining and mature cataracts: A comparison of indocyanine green and trypan blue dyes. Br J Ophthalmol. 2000;84:video report.
14. Chang DF. Clinical comparison of ICG and trypan blue due for mature cataract. Paper presented at: annual meeting of the American Society of Cataract and Refractive Surgery; April 28-May 2, 2001; San Diego, Calif.
15. Pandey SK, Werner L, Vroman DT, Apple DJ. Dye-enhanced anterior capsulorrhexis: Surgical techniques, guidelines, and recommendations for surgeons. Comp Ophthalmol Update. 2003;4:179-185.
16. Wakabayashi T, Yamamoto N. Posterior capsule staining and posterior continuous curvilinear capsulorrhexis in congenital cataract. J Cataract Refract Surg. 2002;28:2042-2044.
17. Guo S, Caputo A, Wagner R, DeRespinis P. Enhanced visualization of capsulorrhexis with indocyanine green staining in pediatric white cataracts. J Pediatr Ophthalmol Strab. 2003;40:268-271.
18. Saini JS, Jain AK, Sukhija J, et al. Anterior and posterior capsulorrhexis in pediatric cataract surgery with or without trypan blue dye: Randomized prospective clinical study. J Cataract Refract Surg. 2003;29:1733-1737.
19. Werner L, Pandey SK, Escobar-Gomez M, et al. Dye-enhanced cataract surgery. Part 2: Learning critical steps of phacoemulsification. J Cataract Refract Surg. 2000;26:1060-1065.
20. Dada T, Ray M, Bhartiya P, Vajpayee RB. Trypan-blue-assisted capsulorrhexis for trainee phacoemulsification surgeons. J Cataract Refract Surg. 2002;28:575-576.
21. De Waard PW, Budo CJ, Melles GR. Trypan blue capsular staining to "find" the leading edge of a "lost" capsulorrhexis. Am J Ophthalmol. 2002;134:271-272.
22. Singh AJ, Sarodia UA, Brown L, et al. A histological analysis of lens capsules stained with trypan blue for capsulorrhexis in phacoemulsification cataract surgery. Eye. 2003;17:567-570.
23. Laureano JS, Coroneo MT. Crystalline lens capsule staining with trypan blue. J Cataract Refract Surg. 2004;30:2046-2049.
24. Akahoshi T. Mixing a viscoelastic and a capsular dye. Cataract & Refractive Surgery Today. 2005;March:39-46.
25. Kayikicioglu O, Erakgun T, Guler C. Trypan blue mixed with sodium hyaluronate for capsulorrhexis. J Cataract Refract Surg. 2003;27:970.
26. Marques DM, Marques FF, Osher RH. Three-step technique for staining the anterior lens capsule with indocyanine green or trypan blue. J Cataract Refract Surg. 2004;30:13-16.