Available in Europe and Canada, trypan blue (VisionBlue; D.O.R.C., Zuidland, the Netherlands), a capsule staining solution for mature cataracts, is not obtainable in the US. The FDA's decision to classify VisionBlue® as a drug rather than a medical device has been the subject of much debate. In essence, this classification makes the approval process for the solution significantly more difficult.

VISUALIZATION OF THE CAPSULORHEXIS
David Chang, MD, of Los Altos, CA, explains that the two dyes that have been adopted worldwide for mature cataracts are indocyanine green (ICG) and trypan blue. Neither is FDA-approved for capsular staining, and only ICG is available in the US, where it is approved for retinal, hepatic, and renal angiography. “Errant radial tears in the capsulorhexis significantly increase the risk of posterior capsule rupture during phacoemulsification. They are much more likely to occur when visualization of the capsule is diminished by a poor or absent red reflex,” states Dr. Chang. He adds that capsule dye therefore is also helpful when there is a very brunescent nucleus, when there is diminished corneal clarity, or when vitreous opacities, such as hemorrhage or asteroid hyalosis, are present.

Samuel Masket, MD, of Los Angeles, CA, states that because ICG is FDA-approved, many surgeons are using it off-label to stain the anterior capsule. According to Dr. Masket, the problem with ICG is that it is not as effective as trypan blue in capsular staining. It is also four times more expensive than trypan blue. In addition, ICG has to be reconstituted, or premixed, in surgery, whereas trypan blue comes as a ready-to-use solution. Dr. Chang adds that although both ICG and trypan blue stain the capsule well, the latter results in a more intense and darker staining of the capsule. This would be significant if, for example, there was poor corneal visibility as well. Trypan blue also provides a more persistent staining of the capsule, allowing the surgeon to visualize the capsulorhexis throughout the nucleus emulsification phase. Dr. Chang states that this is very important with mature cataracts, because an intact capsulorhexis margin is more likely to be torn by the second instrument or phaco tip if it cannot be visualized during nuclear emulsification.

OTHER STAINS
In addition to ICG and trypan blue, various other staining agents have been tried with less success. Dr. Chang notes that methylene blue appears to be toxic to the corneal endothelium, and has resulted in several cases of corneal decompensation. Fluorescein has been tried, but because it is a much smaller molecule, it has the disadvantage of penetrating into, and staining the vitreous.

CORNEAL SAFETY
ICG and trypan blue both appear to be safe for the corneal endothelium. Dr. Masket maintains, “Trypan blue has been used in corneal tissue banks to stain the endothelium so that it can be evaluated. So it is considered to be nontoxic to the endothelium, or very minimally toxic.” According to Dr. Chang, there have been no published clinical reports of corneal decompensation attributable to either ICG or trypan blue. Both of these two dyes have actually been used to count endothelial cells on human donor keratoplasty buttons. Dr. Chang cited a report by Gerrit Melles, MD, that the Dutch National Eye Bank had used trypan blue to examine more than 32,000 donor corneas.1 Masayuki Horiguchi, MD, performed a prospective, randomized study of 20 mature white cataracts, using ICG dye in one half, with the other half serving as controls.2 There were no statistically significant differences in postoperative endothelial cell counts, or laser cell-flare photometry.

VISIONBLUE IN THE US
Many surgeons have used VisionBlue in the US, acquired from Europe or Canada. It greatly increases the safety of difficult cases, and the doctors who use it obviously believe it is safe for their patients. Dr. Masket asserts that whenever he uses VisionBlue, he informs his patients that he is using a nonapproved substance; he is doing this because it makes the surgery safer, simpler, and it provides better outcomes. Dr. Masket believes so strongly in VisionBlue that he will continue to use it as long as he mentions sufficient disclaimers to his patients. He is comfortable that what he is doing is in the best interest of his patients.

Dr. Chang notes that unfortunately, randomized studies large enough to demonstrate that capsular dye reduces complications in mature cataracts would be very costly. Dr. Masket adds that the FDA will approve products if there is established literature, but at this time, there is nothing available that would enable the FDA to look at the literature and approve trypan blue for use in this country. Between these issues, and the lag time of FDA studies, it is unlikely that VisionBlue will be sold in the US in the near future. This leaves ICG as the only capsular dye currently available to US surgeons.

David F. Chang, MD, is a Clinical Professor at the University of California, San Francisco, and is in private practice in Los Altos, CA. Dr. Chang will be the discussant for a paper by Namrata Sharma, MD, comparing different capsular dyes at the upcoming AAO meeting in New Orleans, LA. He does not have a financial interest in any of the materials mentioned herein. Dr. Chang may be reached at (650) 948-9123; dceye@earthlink.net
Samuel Masket, MD, is in private practice in Los Angeles, California, and is a Clinical Professor of Ophthalmology at UCLA. He does not have a financial interest in any of the materials mentioned herein. Dr. Masket may be reached at (310) 229-1220; avcmasket@aol.com
Charles W. Leiter, PharmD, FIACP, the owner of Leiter's Pharmacy, in San Jose, California, is a board-certified compounding pharmacist and a Fellow of the International Academy of Compounding Pharmacists. He also serves as a consultant to the Francis I Proctor Foundation at UCSF. Dr. Leiter may be reached at (800) 292-6773; cleiter@leiterrx.com or at booth 4525 at the AAO meeting.
1. Melles G, de Waard P, Pameyer J, Beekhuis, W: Trypan blue capsule staining to visualize the capsulorhexis in cataract surgery. J Cataract Refract Surg 25:7-9, 1999
2. Horiguchi M, Miyake K, Ohta I, Ito Y: Staining of the lens capsule for circular continuous capsulorhexis in eyes with white cataract. Arch Ophthalmol 116:535-537, 1998