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Does the use of trypan blue during phacoemulsification affect the intraocular pressure?N.G. Ziakas, MD; K. Boboridis, MD; E. Nakos, MD; D. Mikropoulos, MD; V. Margaritis, MD; A.G.P. Konstas, MD

Objective: The purpose of the study was to evaluate the effect of trypan blue on intraocular pressure (IOP) after small-incision cataract surgery.

Design: Prospective, randomized study.Participants: Fifteen patients (30 eyes) with bilateral, dense, age-related cataracts.

Patients with glaucoma, ocular hypertension, exfoliation, pigment dispersion syndrome, history of uveitis, recent use of topical or systemic steroids, and previous ocular surgery were excluded. The patients were random-ly assigned to receive trypan blue during cataract surgery for enhancing capsulorrhexis in 1 of their eyes, while in the other eye, trypan blue was not used. Cataract surgery was performed in an identical fashion in both eyes, with a sutureless posterior limbal incision, phacoemulsification, and implantation of a foldable intraocular lens. The same viscoelastic (sodium hyaluronate) was used in all cases and was thoroughly aspirated at the end of the procedure. All patients received a single dose of 250 mg acetazolamide 8 hours after surgery. No other antiglaucomatous agent was used during surgery or postoperatively. The intraocular pressure (IOP) was measured preoperatively and at 24 hours, 1 week, 1 month, and 3 months postoperatively.

Results: IOP values were similar in both groups at all 4 postoperative measurements. There was no statistically signifi-cant difference in postoperative IOP values between the eyes in which trypan blue was used and the control eyes.

The use of trypan blue during small-incision cataract surgery does not have any effect on IOP during the immediate and early postoperative period.

Objet : Évaluation de l’effet du bleu trypan sur la pression intraoculaire (PIO) après une légère incision pour la chirurgie de la cataracte.

Nature : Étude prospective randomisée.Participants : Quinze patients (30 yeux) ayant des cataractes bilatérales denses liées à l’âge.

: Ont été exclus les patients avec glaucome, hypertension oculaire, exfoliation, syndrome de dispersion pigmentaire, histoire d’uvéite, usage récent de stéroïdes topiques ou systémiques et ayant déjà subi une chirurgie oculaire. Les patients ont été assignés au hasard à recevoir du bleu trypan pendant la chirurgie de la cataracte pour améliorer la capsulorrhexis dans un œil seulement. La chirurgie de la cataracte a été pratiquée de façon identique dans les deux yeux, avec incision limbique postérieure sans suture, phacoémulsification et implantation de lentilles intraoculaires pliables. Le même viscoélastique (hyaluronate de sodium) a été utilisé pour tous les cas et aspiré méticuleusement à la fin de la procédure. Les patients ont tous reçu une seule dose de 250 mg d’acétazolamide 8 heures après la chirurgie. Aucun autre agent antiglaucomateux n’a été utilisé pendant ou après la chirurgie. La PIO a été mesurée avant l’opération, puis 24 heures, 1 semaine, 1 mois et 3 mois après. Les données de la PIO furent les mêmes dans les deux groupes à chacune des 4 prises de mesure.

: Il n’y avait pas d’écart significatif de PIO postopératoire entre les yeux traités au bleu trypan et les yeux témoins.

: L’emploi du bleu trypan pendant la chirurgie de la cataracte micro-incisionnelle n’ont aucun effet im-médiat ni dans la première période postopératoire.

A continuous, curvilinear capsulorrhexis, of the anterior capsule is performed in phacoemulsification and other

cataract surgical procedures to allow safe manipulation within the capsular bag.1,2 To visualize the anterior capsule during the performance of the capsulorrhexis, the red fun-dus reflex produced by the coaxial light of the operating microscope is used. When retroillumination is absent or significantly reduced (e.g., in dense cataracts), it may be dif-

ficult to discriminate the anterior capsule from the under-lying lens tissue. Poor visualization of the capsule may result in an incomplete capsulorrhexis, which increases the risk of radial capsule tears towards or beyond the lens equator.

Over the last few years, trypan blue, a single vital dye, has been used in cataract surgery to enable the surgeon to visualize the capsulorrhexis in the presence of a comprom-ised red reflex.3,4 VisionBlue (Dutch Ophthalmic Research

From the 1st Department of Ophthalmology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Originally received June 9, 2008. Revised Nov. 9, 2008Accepted for publication Jan. 9, 2009Published online Apr. 29, 2009

Correspondence to Nikolas G. Ziakas, MD, 93 Metropoleos St., 546 22, Thessaloniki, Greece; nikolasziakas@yahoo.gr

This article has been peer-reviewed. Cet article a été évalué par les pairs.

Can J Ophthalmol 2009;44:293–6doi:10.3129/i09-055

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Center International BV, Zuidland, the Netherlands) is a sterile, dilute solution of trypan blue. Each millilitre of this solution contains 0.6 mg trypan blue, 1.9 mg sodium monohydrogen orthophosphate, 0.3 mg sodium dihydro-gen orthophosphate, 8.2 mg sodium chloride, sodium hy-droxide for adjusting the pH, and water for injection.

The effect of trypan blue on corneal cells, lens epithelial cells, as well as retinal cells, has been evaluated.5–13 However, to our knowledge there are no studies regarding the toxicity or safety of VisionBlue (Dutch Ophthalmic Research Cen-ter International BV) for the trabecular meshwork cells or the possible effect of its use on intraocular pressure (IOP). We conducted a prospective, randomized study to evaluate the effect of trypan blue (VisionBlue, Dutch Ophthalmic Research Center International BV) on IOP after phaco-emulsification and implantation of a foldable intraocular lens (IOL).

METHODS

The study involved 30 eyes of 15 patients with bilateral, dense, age-related cataract scheduled for phacoemulsifica-tion and IOL implantation. Informed consent was obtained from all patients in the study. Exclusion criteria were previ-ous ocular surgery, history of uveitis, recent use of topical or systemic steroids, ocular hypertension, primary or secondary glaucoma, exfoliation, and pigment dispersion syndrome.

Eight patients were men and 7 were women. Their age ranged from 63–83 (mean 72.6, SD 5.7) years. All patients were randomly assigned to receive trypan blue in 1 of their eyes during the surgery, while in the other eye, trypan blue was not used. The second operation for each patient was performed 1–2 months after the first. The same viscoelastic substance (sodium hyaluronate, Healon, Abbott Medical Optics, Abbott Park, Ill.) was used in all procedures.

All patients were operated on by the same surgeon, in the same fashion. Approximately 1 hour before surgery, phenylephrine 5% and tropicamide 0.5% eye drops were instilled at 15-minute intervals. After peribulbar anes-thesia, a superior, 3.0 mm, posterior limbal incision was performed. When trypan blue was to be used, 0.1 mL of aqueous humour was aspirated through a side port, and an air bubble was injected into the anterior chamber in order to prevent water-like dilution. Through a blunt cannula, 0.1 mL of VisionBlue (Dutch Ophthalmic Research Cen-ter International BV) was injected into the anterior cham-ber, which was irrigated 5 seconds later in order to remove any excess colourant and filled with viscoelastic substance. Then, the procedure continued as a routine phacoemulsi-fication procedure. Capsulorrhexis, hydrodissection, and phacoemulsification of the nucleus were followed by aspira-tion of the cortical remnants and cleaning of the capsular bag. A balanced salt solution was used for irrigation. The capsular bag was then expanded with sodium hyaluronate and a foldable acrylic 3-piece IOL implanted in the bag.

The viscoelastic substance was aspirated thoroughly

from the retrolental space and the anterior chamber using an irrigation-aspiration tip. The tip was rotated right, left, and posteriorly, and the viscoelastic substance was circum-ferentially removed from the prelental, as well as from the retroiridal and preiridal, spaces. Finally, the tip was pressed down on the centre of the optic, and the anterior chamber was rinsed for 10 seconds. The incision was left sutureless.

At the end of the surgery a combination of 0.3 mL of gentamycin 40 mg/mL and 0.3 mL of dexamethasone 4 mg/mL was injected under the conjunctiva, 1 drop of in-domethacin was instilled, and the eye was patched. No mi-otic agent was used intracamerally, and no antiglaucomatous agent was instilled immediately after surgery. All patients re-ceived 1 tablet of acetazolamide 250 mg 8 hours after the end of the surgery. Twenty-four hours later, dexamethasone 1mg/mL and chloramphenicol 5 mg/mL eye drops were in-stilled 4 times daily and continued for 3 weeks. There were no intraoperative or postoperative complications.

The baseline IOP was measured by Goldmann applana-tion tonometer 1 day preoperatively. The IOP was meas-ured with the same calibrated applanation tonometer 1 day, 1 week, 1 month, and 3 months postoperatively between 9:00 and 11:00 AM. The ophthalmologist who measured the IOP was masked to the group assignment.

Group comparisons of the preoperative and postopera-tive IOP and the mean IOP changes from preoperative to 24 hours, 1 week, 1 month, and 3 months postopera-tive measurements were made with paired, 2-tailed t tests. A p value of <0.05 was considered statistically significant. Approval for this study was obtained from the AHEPA University Hospital Review Board, and detailed informed consent was obtained from the patients.

RESULTS

The mean preoperative and postoperative IOP values are shown in Table 1. There were no statistically significant differ-ences in preoperative mean IOP or in mean IOP at 24 hours, 1 week, 1 month, and 3 months postoperatively between the eyes that received trypan blue and the control eyes.

Mean IOP changes from preoperative to 24 hours, 1 week, 1 month, and 3 months postoperative measure-ment in the 2 groups of patients are shown in Table 2. The mean IOP decreased in both groups at all 4 postoperative measurements. The difference was statistically significant at

Table 1—Preoperative and postoperative mean intraocular pressure (mm Hg)

Mean (SD) IOP and range

Time With trypan blue Without trypan blue p value

Preoperative 14.27 (3.44), 10–19 14.64 ±(2.58), 10–18 0.772Postoperative 24 hours 12.50 (3.97), 6–19 12.82 (5.13), 8–27 0.938 1 week 12.91 (2.55), 10–17 13.45 (2.11), 9–16 0.611 1 month 12.64 (3.04), 8–18 13.09 (2.12), 9–16 0.745 3 months 12.27 (2.05), 9–15 12.45 (1.92), 9–15 0.803Note: IOP, intraocular pressure.

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1 month in the group without trypan blue and at 3 months in both groups.

However, when compared with each other, the mean postoperative changes of IOP between the 2 groups of pa-tients showed no statistically significant difference in any of the 4 postoperative values (Table 3).

DISCUSSION

Trypan blue is a tissue-staining agent for use as a med-ical aid in cataract surgery in order to increase the visual-ization of the anterior capsule during capsulorrhexis. There have been studies on the safety of VisionBlue (Dutch Ophthalmic Research Center International BV) for cor-neal cells showing that no mid-term endothelial cell dam-age was induced by its intraoperative use for staining the anterior lens capsule at commonly used concentrations.6 A more recent study reported that trypan blue was toxic in vitro to corneal endothelium and corneal fibroblasts at higher concentrations and notably longer exposure times.5 Another study reported that staining the anterior capsule with trypan blue during routine phacoemulsification af-fected the density and viability of the lens epithelial cells.7 Finally, its effect on retinal cells has been evaluated with controversial reported findings.8–12 To our knowledge there are no studies regarding the toxicity or safety of Vision Blue (Dutch Ophthalmic Research Center International BV) for the trabecular meshwork cells and the possible effect of its use on IOP. This is an important topic for future research. The aim of this prospective study was to evaluate the effect of trypan blue on IOP after routine phacoemulsification and IOL implantation.

Thirty eyes of 15 patients with dense, age-related cata-racts were operated on by the same surgeon with the same technique. Patients were randomly selected to receive try-pan blue in 1 of their eyes, while in the other eye trypan blue

was not used. Because viscoelastic substances are known to play a significant role in postoperative IOP spikes as a result of mechanical obstruction of the trabecular meshwork,14 the same viscoelastic substance (sodium hyaluronate) was used in all surgeries to eliminate the probable effect on IOP. According to a standard protocol, the same medications were given to all patients.

Our study had shortcomings. The sample size was small, and randomization was not optimal. The IOP was first measured the next day and not within 8 hours; therefore, it is likely that IOP spikes within that period of time were missed. Finally, although phacoemulsification time and the volume of irrigation fluid used during surgery are factors known to affect IOP,15 they were not analyzed as part of the protocol. On the other hand, as all cataracts were dense, age related, had a poor red reflex, and all underwent a standard technique by a single surgeon with no intraoperative com-plications, it is unlikely that significant differences occurred in these factors.

There were no statistically significant differences between the 2 groups in mean IOP values preoperatively and at 24 hours, 1 week, 1 month, and 3 months postoperatively. Mean IOP decreased in both groups at all 4 postopera-tive measurements. This observation is in accordance with other reported findings that phacoemulsification is associ-ated with a significant long-term reduction of IOP.15,16 Also, comparing the 2 groups in postoperative reduction of IOP, no statistically significant difference was found in any of the 4 postoperative measurements.

In conclusion, despite the limitations of this study, our findings showed that the use of trypan blue during phaco-emulsification does not have any effects on IOP in the im-mediate and early postoperative period.

The authors have no proprietary interest in any aspect of this article.

Table 2—Mean intraocular pressure (mm Hg) change from preoperative to postoperative measurements

Time (postoperative)

Mean (SD) IOP change and range With trypan blue p value*

Mean (SD) IOP change and rangeWithout trypan blue p value*

24 hours –1.77 (3.50), –8 to +4 0.255 –1.82 (4.79), –7 to +11 0.2371 week –1.36 (3.01), –7 to +3 0.164 –1.19 (2.14), –4 to +3 0.0961 month –1.63 (2.80), –6 to +3 0.082 –1.55 (2.02), –4 to +2 0.0293 months –2.00 (2.49), –6 to +2 0.024 –2.19 (1.83), –5 to +2 0.0027*Different from preoperatively.Note: IOP, intraocular pressure.

Table 3—Comparison of mean intraocular pressure (mm Hg) change postoperatively between the 2 groups

Time (postoperative)Mean (SD) IOP change and range

With trypan blueMean (SD) IOP change and range

Without trypan blue p value

24 hours –1.77 (3.50), –8 to +4 –1.82 (4.79), –7 to +11 0.7081 week –1.36 (3.01), –7 to +3 –1.19 (2.14), –4 to +3 0.8501 month –1.63 (2.80), –6 to +3 –1.55 (2.02). –4 to +2 0.9343 months –2.00 (2.49), –6 to +2 –2.19 (1.83), –5 to +2 0.863Note: IOP, intraocular pressure.

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Keywords: intraocular pressure, phacoemulsification, trypan blue