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Bromphenol blue staining in eyes with mature cataract

Haritoglou, Christos MD; Priglinger, Siegfried G.; Strauss, Rupert MD; Gandorfer, Arnd MD; Kampik, Anselm MD

Journal of Cataract & Refractive Surgery: December 2007 - Volume 33 - Issue 12 - p 2155-2157
doi: 10.1016/j.jcrs.2007.07.053
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Capsulorhexis in patients with mature white cataracts can be challenging because of the absence of the red fundus reflex. In these cases, dye-enhanced cataract surgery has become the preferred method to enable the surgeon to perform a controlled continuous curvilinear capsulorhexis (CCC) of the anterior capsule. Several dyes have been used, among them fluorescein, indocyanine green, and trypan blue.1–3 The latter is currently the most frequently used dye; the concentrations used to stain the capsule vary between 0.0125% and 0.1%.1,4,5 Trypan blue has a good long-term safety profile.6

In previous experimental studies,7–9 we investigated several vital dyes in vivo and in vitro to evaluate their staining characteristics and safety. These studies showed that bromphenol blue (tetrabromophenolsulfonephthalein) stained the anterior capsule well and was also safe for intraocular application. Before bromphenol blue was used in humans, its toxicity had been thoroughly investigated in experimental settings, including ex vivo cell culture models and in vivo animal studies with intraocular exposure times up to 7 days.7–9 Clinical examination of the animals during the 7-day period of dye exposure did not reveal any signs of inflammatory response or toxicity in the anterior segment of the eye; no corneal edema was seen even after injection of high dye concentrations and no histological abnormalities were seen following enucleation.7 The data obtained from these toxicity studies underline the biocompatibility of bromphenol blue, which has been used as a vital stain to probe the blood–brain barrier as a protein stain and as a pH indicator.10

We recently reported the use of bromphenol blue in vitreoretinal surgery.11,12 In the present report, we describe our experience using bromphenol blue to stain the human lens capsule in patients with white cataracts. This investigation was approved by the local ethics committee and the Institutional Review Board. Written informed consent was obtained from all patients before surgery.

Five consecutive patients were included in this preliminary series of patients. The mean age of the 3 women and 2 men was 59 years. Preoperatively, the visual acuities were 20/400 or worse. Cataract formation was due to ocular trauma (2), uveitis (1), and unknown cause (2). All patients had a complete clinical examination before surgery. B-scan ultrasound of the globe was performed to rule out intraocular pathologies such as tumors or retinal detachments.

Bromphenol blue powder was dissolved and diluted using fortified balanced salt solution (BSS Plus) and sterilized using a 0.22 μm syringe filter. Dye concentrations of approximately 0.1% (310 mOsm, pH 7.6) were used. In 3 eyes, the dye was injected into an air-filled anterior chamber and carefully removed by injection of an ophthalmic viscosurgical device (OVD) (Figure 1) immediately after; in 2, it was injected after the anterior chamber was filled with an OVD without prior air injection. In the latter case, the dye was evenly and gently distributed on the lens surface using the cannula and excessive dye was removed after completion of the CCC (approximately 1 minute after application). Both techniques allowed predictable and uniform staining of the anterior capsule due to the direct contact of the dye with the capsule.

Figure 1
Figure 1:
A: Bromphenol blue dye is injected into the air-filled anterior chamber. B: After the OVD is injected, dark, evenly distributed staining of the anterior capsule is observed. C: A CCC shows the contrast between the stained capsule and the white cataract.
Figure 1
Figure 1:
(continued)
Figure 1
Figure 1:
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A CCC was performed in 4 patients using a bent needle. In 1 patient, the capsule was very rigid and had to be opened with an intraocular forceps. Excellent contrast between the white lens and the stained capsule was noted in all patients. The dye did not penetrate the capsule. There was no unwanted staining of other tissues such as the iris or corneal endothelium. During surgery, staining of the limbal incision through which the dye had been injected was observed; this disappeared shortly after dye application.

One day postoperatively, no residual dye was detected on the remaining rim of the anterior capsule or any other ocular tissue. All patients were followed up to 5 months. The mean visual acuity was 20/50, and no complications such as corneal edema, signs of inflammation, or relevant decrease in corneal endothelial cells were seen.

We are aware that the number of patients is small. This report does not represent a toxicity study for the application in the anterior segment but an observational case series. The dye applied had been carefully evaluated prior to its use in humans. The concentration used during cataract surgery (0.1%) was lower than the concentration reported to be safe for vitreoretinal surgery (0.2%).11,12

Based on our experience with vitreoretinal surgery11,12 and the present observations, we are confident that bromphenol blue can be safely used in anterior segment surgery. However, before its routine use can be recommended, additional studies addressing the question of toxicity in the anterior segment and clinical investigations with more patients must be performed. As the staining effect seen in our patients was strong, we think the concentration of the dye can be reduced.

REFERENCES

1. Melles GRJ, de Waard PWT, Pameyer JH, Beekhuis WH. Trypan blue capsule staining to visualize the capsulorhexis in cataract surgery. J Cataract Refract Surg. 1999;25:7-9.
2. Fritz WL. Fluorescein blue, light-assisted capsulorhexis 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 curvilinear capsulorrhexis in eyes with white cataract. Arch Ophthalmol. 1998;116:535-537.
4. Yetik H, Devranoglou K, Ozkan S. Determining the lowest trypan blue concentration that satisfactorily stains the anterior capsule. J Cataract Refract Surg. 2002;28:988-991.
5. Jacob S, Agarwal A, Agarwal S, et al. Trypan blue as an adjunct for safe phacoemulsification in eyes with white cataract. J Cataract Refract Surg. 2002;28:1819-1825.
6. Norn MS. Vital staining of corneal endothelium in cataract extraction. Acta Ophthalmol (Copenh). 1971;49:725-733.
7. Haritoglou C, Yu A, Freyer W, et al. An evaluation of novel vital dyes for intraocular surgery. Invest Ophthalmol Vis Sci. 2005;46:3315-3322.
8. Schuettauf F, Haritoglou C, May CA, et al. Administration of novel dyes for intraocular surgery: an in vivo toxicity animal study. Invest Ophthalmol Vis Sci. 2006;47:3573-3578.
9. Haritoglou C, Tadayoni R, May CA, et al. Short-term in vivo evaluation of novel vital dyes for intraocular surgery. Retina. 2006;26:673-678.
10. Horobin RW, Kiernan JA, editors., Conn's Biological Stains; a Handbook of Dyes, Stains and Fluorochromes for Use in Biology and Medicine, 10th ed., BIOS Scientific Publishers, Oxford, UK, 2002, pp. 215-216.
11. Haritoglou C, Schumann RG, Strauss R, et al., 2007. Vitreoretinal surgery using bromphenol blue as a vital stain: evaluation of staining characteristics in humans In press, Br J Ophthalmol, 91, 1125-1128.
12. Haritoglou C, Strauss R, Priglinger SG, et al. Delineation of the vitreous and posterior hyaloid using bromphenol blue. In press. Retina 2007.

SUPPLEMENTARY DATA

Supplementary data associated with this article can be found in the online version, at doi:10.1016/j.jcrs.2007.07.053

© 2007 by Lippincott Williams & Wilkins, Inc.