Comparing the efficacy of mydriatic cocktail-soaked sponge and conventional pupil dilation in patients using tamsulosin – a randomized controlled trial

Proper perioperative mydriasis and anaesthesia are prerequisite to successful cataract surgery.

Cataract operation may be performed using different preoperative protocols which should be determined according to the needs and preference of the patient, the anaesthesia professionals and the surgeon [1]. Adequate pupil dilation is even more crucial for patients who are at risk of limited pupillary function.

Intraoperative floppy iris syndrome (IFIS) associated with tamsulosin – a systemic α₁ adrenergic receptor antagonist (α1-ARA) - was first described by Chang and Campbell in 2005. It is characterised by the triad of (1) flaccid iris stroma that undulates and billows in response to ordinary intraocular fluid currents, (2) tendency for the iris stroma to prolapse towards the phaco and side-port incisions, and (3) a progressive intraoperative pupillary miosis during cataract surgery [2].

IFIS may lead to the constriction of the surgical field which increases vision-threatening complications of cataract surgery such as iris stroma damage, posterior capsular rupture, and loss of vitreous, particularly when surgeons are unaware of patient’s medical history [3–5].

Systemic α-blockers are used to treat the urinary symptoms of benign prostatic hypertrophy (BPH). These agents relax smooth muscle in the prostate and bladder. This effect is utilized to improve symptoms associated with BPH [6, 7]. However, this α-blockade can influence iris motility also.

A strong association was found between IFIS and tamsulosin [8] – a selective α_1A and α_1D adrenergic receptor antagonist, which is a common therapeutic option for BPH. Several studies showed a risk of IFIS as high as 53.3%-93.8% with tamsulosin use [2, 9–14].

Various strategies were advocated for patients taking α1-ARA to achieve appropriate mydriasis and to overcome the progressive miosis such as: preoperative topical atropine, intracameral injection of epinephrine, careful wound construction, mechanical pupil dilation, gentle hydrodissection, low-flow fluidic settings, and bimanual irrigation-aspiration [15–17].

Preoperative discontinuation of α₁ adrenergic receptor antagonist medication has an unclear role in inhibiting the occurernce of IFIS [2, 5, 12, 17–20].

All of the above techniques serve as preventive measures to minimize the risk of IFIS, however they do not eliminate its occurrence.

Previous studies indicated that the use of a wick pre-soaked in standard mydriatic and non-steroidal anti-inflammatory drugs was as effective or superior to the conventional repeated instillation of drops before cataract surgery in a mixed cohort [21–24].

In our study we investigated the efficacy of a mydriatic cocktail-soak sponge as an alternative method to achieve satisfactory pupil dilation in high risk patients taking tamsulosin.

Mean age ± standard deviarion (SD) was 78.60 ± 10.35 years in group 1, 76.64 ± 6.85 years in group 2, and 78.48 ± 5.84 in group 3. One way ANOVA showed no significant age difference between the three groups (p = 0.5777).

No adverse effect related to mydriatic-sponge use was experienced.

One way ANOVA test did not show significant difference in pupillary diameter between groups preoperatively (p = 0.079) and after nucleus delivery (p = 0.123), however we found significant difference before IOL implantation (p = 0.0291).

We found no significant difference between the three groups in miosis 1 (p = 0.4763), miosis 2 (p = 0.0760) and in miosis total (p = 0.1678).

In the two tamsulosin treated groups, the patients dilated with a mydriatic wick had greater preoperative mydriasis in comparison with patients receiving conventional eyedrops regimen, however, this difference was not significant. This slight difference disappeared at later stages of surgery.

There was even distribution of temporal and oblique clear corneal incision in all 3 groups.

In group 1, iris retractors were used before completing nucleus delivery in a single case and two additional cases after nucleus delivery. In group 2, we retracted iris with hooks in two patients after clear corneal incisions. In group 3, we had to facilitate surgery by using iris retractors with a patient before completing nucleus delivery.

IFIS signs were observed in a significantly higher degree in group 1 compared with group 3.

Minor (3/30, 2/28 and 1/31 respectively) and major (1/30, 0/28 and 0/31 respectively) complication rate was similar in all groups.

Mean operation time was shorter in group 3 (15.26 ± 3.21 minutes) than in the two tamsulosin treated groups (15.87 ± 3.21 minutes and 16.61 ± 2.59 minutes) respectively, but the difference was not significant (p = 0.1547).

Cataract surgery is more challenging in patients taking α1-ARA due to poor and unstable perioperative mydriasis [2, 6, 8, 16]. History of tamsulosin use among patients undergoing cataract surgery was estimated around 3% in the United States [25–27]. Although several pre- and intraoperative methods are used to overcome this problem, IFIS remains one of the pitfalls of cataract surgery.

In our study we investigated the efficacy of mydriatic cocktail-soaked sponge pupil dilation in patients using tamsulosin due to benign prostatic hypertrophy. Our results indicated that regardless of the preoperative protocol, patients with tamsulosin treatment show poorer perioperative mydriasis in comparisons with control subjects.

Comparing the two groups having the mydriatic cocktail-soaked sponge pupil dilation preoperatively (group 1 vs. group 3), patients with tamsulosin treatment showed significantly smaller pupil diameters after nucleus delivery and before IOL implantation but not preoperatively.

Patients in group 1 showed significantly higher degree of miosis between our second and third pupil measurement (miosis 2) in comparison with group 3 (p = 0.024). These findings are consistent with the fact that patients with tamsulosin treatment develop progressive intraoperative pupillary miosis during cataract surgery [2, 3, 10]. In contrast, Casuccio et al. found that pupil diameter was significantly smaller both preoperatively and postopoperatively in patients taking tamsulosin compared with their control group, however both exclusion criteria and their mydriatic regimen were different [27].

We had a uniform distribution of oblique and temporal wounds in each group, which limits observational bias between groups. It has been shown that the anterior chamber is deeper superiorly than temporally, and therefore a superior approach may be preferred in some cases to minimize the risk or iris prolapse [28, 29]. However there is a general consensus that meticulous wound construction – 2-step or 3-step incision, appropriate lenght of the wound, and the location of entry into the anterior chamber in relation to the iris plane – is essential in preventing intraoperative iris prolapse [29–32].

The incidence of iris prolapse was similar in our two tamsulosin treated group (23% and 25% respectively). This incidence is lower that in the largest prospective study (n = 167) published to date [10], however α1-ARA medication is only one of the many predisposing factors [29]. Iris billowing – a hallmark of IFIS – was found in similar percentage in the two tamsulosin treated group as in two previous studies [11, 24].

The frequency of iris retractors use was similar in the two tamsulosin groups (3/30 vs. 2/28), and lower than in the previously pubished results of Blouin et al., and Issa et al. 42.6% and 38% respectively [12, 33].

Minor complication rate was higher in the two tamsulosin treated groups (10% and 7.1%) than in the control group (3.2%), however this difference was not significants which is probably due to the low sample size. A single patient treated with tamsulosin had posterior capsule rupture without vitreous loss in group 1. Patients having minor or major complications did not have significantly smaller preoperative pupillary diameter. Minor complication rate was similar as in the recently published studies, however lower than in earlier studies; this is probably due to the increasing awareness of IFIS and to our unmasked study fashion [2, 3, 10, 14, 27, 34, 35]. The relatively high incidence of minor complication in the control group might be related to small sample size or to the high prevalance of systemic hypertension, which was proposed as a possible cofounder of IFIS [13].

We use mydriatic cocktail-soaked sponge pupil dilation as a standard method in our cataract surgery protocol. In our practice, the use of mydriatic sponge beside the effective intraoperative mydriasis also gives considerable saving in nursing resources along with medicine expenses, in comparison with conventional repeated eyedrops method. We observed that this method is as effective as the conventional drop regimen in a mixed case cohort (unpubished results), but we have not found any previous publication indicating that this method may be suitable for high risk patients such as patients taking tamsulosin.

Our results show that the sponge was as effective in achiving sufficient periopereative mydriasis in tamsulosin treated patients as the conventional repeated eyedrops method. The use of mydriatic soaked sponge was not associated with any advers effect, and showed similar rate of minor complications as found in the conventional repeated eyedrops group.

Previously, three randomised controlled studies investigated the use of mydriatic drug delivery by a soaked wick placed in the lower fornix [22–24]. In all these studies, similar exclusion criteria were applied as in our study, however, in the first study patients with diabetes and very dark irides, and in the latest study, patients with systemic hypertension and ischemic heart disease were also excluded. These studies did not registered the use of α1-ARA medicines.

Only the study by McCormick indicated a clear timeframe for pupil dilation: the pledget sponge was removed after 20 minutes. In our protocol, we terminated pupil dilation 30 minutes after initiation.

In the first study preoperative pupil diamater was measured 1–4 hours after initiation of pupil dilation with a wick soaked in mydriatic drops (Tropicamide 1%, Phenilephine 2.5% and Diclophenac sodium 0.1%), but no intraoperative measurement was taken. In the second study horisontal pupil diamater was measured in milimeters prior to surgery, and 40 minutes after commencement of mydriatic regime (Tropicamide 1%, Phenylephrine 2.5% and Atropine 1%) without any intraoperative pupil assesment. In the latest study pupillary diameters were measured 15, 30, 45 minutes after placing in the lower fornix a sponge - immersed in the cocktail regiment consisting of 1:1:1:1 ratio of 2.5% phenylephrine, 0.5% moxifloxacin, 1% cyclopetolate and 0.03% flurbiprofen eye drops. Pupil size was also assessed intraoperatively after nucleous delivery and IOL implantation.

Preoperative pupil diameter was higher in the study by Dubois et al., similar to McCormick et al. and lower in by Sengupta et al. than in our study, however all three studies used different mydriatic cocktail regime and duration of sponge use. We observed similar pupil diameters after nucleous delivery as in the latest study (6.20 mm).

The study by Dubois et al. and McCormick et al. found that the cocktail-soaked sponge protocol leads to similar results as the conventional drop application. The study by Sengupta et al. showed that results were superior with the soaked-wick method.

Our study group of tamsulosin patients had much higher risk of developing progressive intraoperative miosis - a component of IFIS - than a mix cohort. Various studies indicated up to hundred times higher incidence of IFIS in patients with α1-ARA medication. None of the previous three studies investigated the presence of IFIS or intraoperative complications.

Pupil dilation by mydriatic cocktail-soaked sponge showed to be effective in all three studies without any adverse event that might be related to the use of sponge. The sponge primarily used to absorb and drain blood and fluid from the surgical field during ophthalmic procedures, but alternatively it serves as mydriatic and anaesthetic reservoir from which drugs diffuse down along its concentration gradient into the ocular tissues.

Our study has certain limitations. First surgeons were not masked to use of tamsulosin due to institutional quality regulations that require the preoperative checking of patient medication, which may lead to observational bias. Second, the detection of IFIS (iris billowing) relied on surgeon’s subjective assessment, however this limitation is common in most studies, and the incidence of IFIS in our study was similar to previous findings. Third, we had a relatively small sample size which might have an impact on statistical analysis, however the number of tamsulosin treated subjects in our study was similar to most studies published so far.

In conclusion we have found that using a mydriatic cocktail-soaled wick – an alternative way to achieve intraoperative mydriasis for cataract surgery – was as effective and safe as the conventional repeated eyedrops regiment in tamsulosin using patients. Though this method did not provide clinical difference or benefit compared to the conventional method, it may serve as a safe and timesaving alternative preoperative protocol even for high risk tamsulosin treated patients.