Redilatation with intracameral mydriatics in phacoemulsification surgery

Authors


Gunnie Bäckström MD
Eye Clinic
Örnsköldsviks Hospital
SE-890 89 Örnsköldsvik
Sweden
Tel: + 46 660 89 000
Fax: + 46 660 89 259
Email: gunnie.backstrom@lvn.se

Abstract.

Purpose: To determine whether intracameral mydriatics can redilate pupils that contract during phacoemulsification cataract surgery.

Methods: A total of 80 patients were included in this prospective, randomized, double-blind study performed at Örnsköldsviks Hospital Eye Clinic. Of these, 60 patients had 0.6 µg/ml of epinephrine added to the balanced salt solution (BSS) used for irrigation and 20 patients did not. The patients in each group were randomized and given either an intracameral mydriatics (ICM) solution or placebo intracamerally after phacoemulsification and cortex cleaning. The pupil size was registered preoperatively, after cortex cleaning, 30 seconds after study injection, 2 mins after study injection and the day after surgery.

Results: No clinically relevant differences were found preoperatively. In the epinephrine material a significantly longer operation time (p = 0.023) and more procedures requiring Vision Blue™ and Kelman-type tip in the placebo group might indicate diversity in the grade of cataract. There was a greater degree of contraction in the absence of epinephrine in the irrigation solution (2.3 ± 1.0 mm in the ICM group and 3.2 ± 0.7 mm in the placebo group) compared to in the presence of epinephrine. With no epinephrine ICM significantly redilated the pupils at 30 seconds (p ≤ 0.001) as well as at 2 mins (p = 0.015).

Conclusion: We have shown that in cases with an intraoperative pupil contraction, ICM is effective in redilating the pupil. Insufficient adrenergic stimulation of the pupil dilator appears to be a major factor causing intraoperative pupil contraction during phacoemulsification cataract surgery.

Introduction

The rate of cataract surgery has been constantly increasing (Lundstrom et al. 2002) and the progression towards fewer postoperative controls (Edwards et al. 1997), shorter periods of hospitalization (Oshika et al. 2001) and outpatient surgery (Yi et al. 2001) at significantly lower cost (Castells et al. 2001) have required the improvement of surgical techniques.

In the continuous development of cataract surgery procedures, the topic of preoperative pupil dilatation has recently taken some new steps. Intracameral mydriatics (ICM) has been evaluated as an alternative to traditional topical mydriatics in phacoemulsification surgery, with the first study of ICM (Lundberg & Behndig 2003) concluding that it is a rapid, effective and safe method. A clinical evaluation (Behndig & Eriksson 2004) confirmed the benefits from the method when used in high volume surgery.

Surgically induced miosis commonly occurs during cataract extraction surgery (Gimbel 1989) due to mechanical manipulation of the iris affecting the sensitive dilator muscle (Moller et al. 2000). The induced miosis is significantly more pronounced in diabetes patients undergoing cataract surgery (Zaczek & Zetterstrom 1997). To perform a safe operation the pupil needs not only to be dilated preoperatively but preferably to remain dilated throughout the procedure. Different techniques have been suggested for the maintenance of mydriasis (Duffin et al. 1982), including preoperative diclofenac (Antcliff & Trew 1997), naproxen (Papa et al. 2002), viscous phenylephrine hydrochloride (Duffin et al. 1983a) or intraoperative intracameral epinephrine, either in the irrigation solution (Liou & Yang 1998) or as a single bolus dose (Liou & Chen 2001).

Other investigators (Duffin et al. 1983b) have suggested that in cases when the pupil contracts during surgery, it might be possible to redilate the pupil with an intracameral injection of an appropriate dilating substance. The purpose of this study was to evaluate whether an intracameral mydriatics solution can redilate pupils that contract during phacoemulsification cataract surgery.

Material and Methods

This prospective, randomized, double-blind study was approved by the research ethics committee of Umeå University, Umeå, Sweden. A total of 80 consecutive patients with age-related cataracts, with planned unilateral phacoemulsification and intraocular lens (IOL) implantation, were included after informed consent had been gained.

All patients were given topical mydriatics consisting of three drops of a mixture of cyclopentolate 0.85% and phenylephrine 1.5%. Three drops of tetracaine 1% for surface anaesthesia were administered at a point 5 mins after this and 5 mins prior to surgery. All procedures were performed by one surgeon (GB). At the beginning of the procedure, all patients were given 150 µl of preservative-free xylocaine 1% intracamerally.

The first 60 patients had 0.6 µg/ml epinephrine added to the balanced salt solution (BSS) used for irrigation and the subsequent 20 patients did not. All subjects were randomized to receive either ICM 150 µl cyclopentolate 0.1%, phenylephrine 1.5% and xylocaine 1% intracamerally, or placebo (150 µl of BSS intracamerally) after phacoemulsification and cortex cleaning. The sterile ICM solution was prepared by the Product and Laboratory Department of the Swedish Pharmacy (Apoteksbolaget AB, Umeå, Sweden) from sterile salts, as previously detailed (Lundberg & Behndig 2003). The list of randomization was prepared by the research and development department (FoU Centrum, Sundsvall, Sweden) at the county council. Once each patient had been included by the surgeon and given a study number, the nurse in the preoperative room consulted the list of randomization and then informed the surgical assistant whether the patient was to be given ICM or placebo. The injections were then prepared in a double-masked fashion by the surgical assistant in a non-marked syringe prior to the patient and surgeon entering the operating theatre.

The surgical technique involved a temporal corneoscleral incision, a Sovereign® with WHITESTAR™ Technology phacoemulsificator (Advanced Medical Optics, Santa Ana, CA, USA, with standardized settings and microtips, and DuoVisc® (Alcon Laboratories, Fort Worth, TX, USA) as viscoelastic agent. An ACRYSOF® SA60AT foldable IOL (Alcon Laboratories) was implanted with an injector in all cases. Postoperatively prednisolone 0.5% was given three times daily for 3 weeks. No extra intraocular pressure (IOP) reducing agents were given postoperatively. Glaucoma patients, however, continued with their ordinary medication.

The pupil sizes were registered at the beginning of the procedure, after cortex cleaning, 30 seconds after study injection and approximately 2 mins after study injection (when the IOL had been prepared in the injector). The registration technique from the video recordings has been described previously (Lundberg & Behndig 2003). In the present study, a 2.5-mm slit knife was used, and the pupil diameters (in mm) were calculated as (mean pupil diameter/blade width) × 2.5. One day postoperatively, the pupil diameters were measured with callipers.

Preoperative registrations included the age and sex of all subjects, the best corrected visual acuity (BCVA) with values < 0.1 registered as 0.1, IOP and the presence of pseudoexfoliations, glaucoma, pilocarpine medication and diabetes. Intraoperatively, the total operation time, ultrasound time and energy and effective phaco time (EPT) were registered, as well as any complications. The subjective surgical performance during phacoemulsification, cortex aspiration and lens implantation was graded on a scale of 0−2, where 0 = uncomplicated, 1 = slightly complicated and 2 = complicated performance (Behndig & Eriksson 2004). The day after surgery, visual acuity and IOP were registered. In addition, the inflammatory reaction and corneal swelling were graded at the slit-lamp examination by the surgeon on a scale of 0−2, where 0 = a mild reaction/swelling seen in many cases postoperatively, 1 = intermediate and 2 = pronounced postoperative reaction/swelling (Behndig & Eriksson 2004).

Thirteen patients were excluded from the study. Five patients declined to participate. Four patients had a posterior capsule rupture with use of Viscoat© (Alcon Laboratories) to hold back the vitreous, the viscoelastic agent thus being a mechanical obstacle to free pupil movement. Three patients had loose lenses (two in combination with insufficient preoperative dilatation of the pupil) with use of iris hooks in the pupil and the capsulorhexis; all three also had capsular tension rings. The iris hooks were naturally considered a mechanical obstacle to free pupil movement. One patient was excluded because of technical problems with the video recording.

For comparisons of means, the statistical analyses were made with Student's two-tailed t-test. To check for preoperative differences in sex, presence of pseudoexfoliations, glaucoma and pilocarpine medication Fisher's exact test was used, as well as for the subjective scoring of surgical performance and postoperative reactions with the exception of corneal swelling in the epinephrine group because spss does not support Fisher's exact test for more than 2 × 2 tables. Here, Pearson's chi-squared test was used. A p-value of < 0.05 was considered statistically significant.

Results

There were no preoperative differences between the ICM and placebo groups with the exception of higher preoperative IOP in the placebo group in the non-epinephrine material (p = 0.013), but the IOPs were within normal limits in both groups (Table 1). The operation times were significantly shorter (p = 0.023) in the ICM group in the epinephrine material. There were no significant differences in EPT (Table 2), but in the placebo group more cases required Vision Blue™ and Kelman-type tip (Table 3).

Table 1.  Selected preoperative parameters.
ParameterEpinephrine groupNon-epinephrine group
 IntracameralPlacebopIntracameralPlacebop
 mydriatics  mydriatics  
  1. Means ± SD, except *, frequency in percent.

  2. P-values calculated with Student's two-tailed t-test, except *, Fisher's exact test.

Number of eyes3030 1010 
Age, years74 ± 1175 ± 110.93376 ± 1180 ± 80.417
Sex (female)*53.3%56.7%1.00050.0%50.0%1.000
Pseudoexfoliations*20%40%0.15820%20%1.000
Glaucoma*26.7%26.7%1.0000%20%0.474
Pilocarpine medication*6.7%0%0.4920%0% 
Diabetes*10%23.3%0.29920%20%1.000
Preoperative IOP15.1 ± 3.816.0 ± 3.90.36713.3 ± 2.916.7 ± 2.60.013
Table 2.  Selected perioperative parameters.
ParameterEpinephrine groupNon-epinephrine group
 IntracameralPlacebopIntracameralPlacebop
 mydriatics  mydriatics  
  1. Means ± SD. P-values calculated with Student's two-tailed t-test.

Number of eyes3030 1010 
Surgical time (mins)15.9 ± 3.518.5 ± 5.10.02315.8 ± 1.820.9 ± 7.10.052
Effective phaco time (seconds)9.2 ± 7.711.5 ± 12.20.3817.6 ± 5.49.2 ± 4.70.491
Preoperative pupil size (mm)6.8 ± 1.06.5 ± 1.20.1756.7 ± 1.17.0 ± 1.10.549
Pupil size after cortex cleaning (mm)6.4 ± 1.05.9 ± 1.10.0614.4 ± 1.13.8 ± 0.80.168
Pupil contraction (mm)0.4 ± 0.50.6 ± 0.40.2012.3 ± 1.03.2 ± 0.70.025
Pupil size at 30 seconds (mm)6.4 ± 1.05.8 ± 1.20.0465.3 ± 1.43.5 ± 0.90.003
Redilatation at 30 seconds (mm)0.01 ± 0.2− 0.03 ± 0.20.3520.9 ± 0.7− 0.3 ± 0.4< 0.001
Pupil size at 2 mins (mm)6.1 ± 1.06.0 ± 1.20.6574.7 ± 1.23.5 ± 0.80.013
Redilatation at 2 mins (mm)0.4 ± 0.30.1 ± 0.2< 0.0010.3 ± 0.6− 0.3 ± 0.40.015
Intraocular pressure day 119.6 ± 8.723.6 ± 11.60.13714.8 ± 4.925.8 ± 15.70.058
Change in BCVA0.2 ± 0.30.2 ± 0.30.7730.03 ± 0.30.09 ± 0.30.647
Pupil size day 16.4 ± 1.73.6 ± 0.9< 0.0016.2 ± 1.33.3 ± 0.9< 0.001
Table 3.  List of complications and complicating factors.
ParameterEpinephrine groupNon-epinephrine group
 IntracameralPlaceboIntracameralPlacebo
 mydriatics mydriatics 
Number of eyes30301010
Capsular tension ring and/or
iris hooks in capsulorhexis1200
Use of Vision Blue™1300
Hard nucleus (with use
of Kelman-type tip)1400

Prior to the study injections there were no significant differences in pupil measurements between the ICM and the placebo groups but significantly larger pupil contractions were noted in the placebo group (p = 0.025) in the non-epinephrine material. It was also notable that pupil contractions in the non- epinephrine material were 2.3 ± 1.0 mm (ICM group) and 3.2 ± 0.7 mm (placebo group), while in the epinephrine material, they were 0.4 ± 0.5 mm (ICM group) and 0.6 ± 0.4 mm (placebo group) (Table 2).

In the epinephrine material 30 seconds after study injection there were significantly larger pupils in the ICM group (p = 0.046) but no significant redilatation (0.01 mm in the ICM group and− 0.03 mm in the placebo group, the later consequently a continued contraction). Somewhat surprisingly, at 2 mins after injection, there was a significance in favour of the placebo group (− 0.4 mm in the ICM group compared with 0.1 mm in the placebo group, p ≤ 0.001) (Fig. 1). Thus the ICM group had contracted, whilst the placebo group had started to dilate (Table 2).

Figure 1.

Boxplot of redilatation, at 30 seconds and at 2 mins in the groups with epinephrine added to the BSS irrigation solution and with no epinephrine added to the BSS irrigation solution. Means (mm) and quartiles. Negative values represent contractions.

However, in the non-epinephrine material 30 seconds after injection, there was a significantly larger pupil (p = 0.003) as well as a significant redilatation (p ≤ 0.001) in the ICM group compared to the placebo group. Furthermore, 2 mins after injection there was significance in pupil measurements (p = 0.013) and redilatation (p = 0.015) in favour of the ICM group (Table 2; Fig. 1).

The only occasion on which significantly larger pupils were seen in the ICM group compared to the placebo group in both the epinephrine and non-epinephrine subjects was at the pupil size measurement on day 1 after surgery (p ≤ 0.001 in both materials) (Table 2). No significant differences were seen in surgical performance or postoperative reactions (Table 4).

Table 4.  Surgical performance and postoperative reactions.
ParameterEpinephrine group
 Intracameral mydriaticsPlacebop
Number of eyes30  30   
Ranking (% of eyes)012012 
Phacoemulsification93.36.7083.316.700.424
Cortex aspiration96.73.3086.713.300.353
Lens implantation1000083.316.700.052
Conjunctival injection9010096.73.300.612
Corneal swelling76.7203.363.3306.70.518*
Cells/flare96.73.30100001.000
ParameterNon-epinephrine group
 Intracameral mydriaticsPlacebop
  1. Surgical performance during different parts of the procedure ranked as 0 = uncomplicated, 1 = slightly complicated and 2 = complicated performance.

  2. Postoperative reactions by slit-lamp examination at day 1 after surgery ranked as 0 = insignificant, 1 = intermediate and 2 = pronounced reaction/swelling.

  3. The table presents the percentage of eyes in each category. P-values were calculated with Fisher's exact test, except *, Pearson chi-squared test.

Number of eyes10  10   
Ranking (% of eyes)012012 
Phacoemulsification10000901001.000
Cortex aspiration10000703000.211
Lens implantation1000010000 
Conjunctival injection1000010000 
Corneal swelling90100802001.000
Cells/flare1000010000 

Discussion

We have shown that intracameral mydriatics can redilate pupils which contract during phacoemulsification surgery. The difference in contraction between the epinephrine and non-epinephrine materials demonstrated here is in accordance with results reported previously (Gimbel 1989). The significantly larger degree of contraction in the placebo group in the non- epinephrine material might be a consequence of the tendency towards longer operation times in the placebo group (p = 0.052), possibly with more mechanical manipulation of the iris (Moller et al. 2000).

In the presence of epinephrine in the irrigation solution the ICM failed to significantly redilate the pupils at 30 seconds and at 2 mins, although the pupils in the ICM group were significantly larger at 30 seconds after the study injections. In fact there was significance in favour of the placebo group at 2 mins, but with a redilatation of 0.1 ± 0.2 mm from an initial pupil size of 5.9 ± 1.1 mm that is likely to be of minor clinical importance. In the absence of epinephrine in the irrigation solution, the significant redilatation in the ICM group at 30 seconds (p ≤ 0.001) as well as at 2 mins (p = 0.015) supports insufficient adrenergic stimulation as being a major factor causing intraoperative pupil contraction during phacoemulsification cataract surgery.

The shorter operation time in the ICM group in the epinephrine material might indicate diversity in the grade of cataract between the ICM group and the placebo group, but there were no significant differences in EPT supporting this. However, the more frequent use of Vision Blue™ and Kelman-type tip could point to a slight difference in the maturity of the cataract between the groups.

Intracameral mydriatics renders larger pupils at day 1 after surgery, as has been shown previously (Lundberg & Behndig 2003). This is also true in cases with epinephrine in the irrigation solution, but as there are no significant differences in the change in BCVA it does not seem to affect visual restoration, in accordance with earlier studies (Behndig & Eriksson 2004). This extended effect, however, might reduce the miotic effect of intraoperative acetylcholine, compared to when epinephrine only is used in the irrigation solution (Elliot & Carter 1989). This possible effect of ICM, however, will need to be studied separately.

Acknowledgements

The authors wish to thank the R & D Department for statistical support and also the skilful staff at the Eye clinic, Örnsköldsviks Hospital.