Purpose
To assess pupil dynamics quantitatively in relation to the use of α 1 -adrenoceptor antagonists, which contribute to the features of intraoperative floppy iris syndrome, using a new, hand-held, digital pupillometer.
Design
Prospective case-control study.
Methods
We studied 15 and 25 patients administered tamsulosin and alfuzosin, respectively, as well as 25 control patients. Resting pupil diameter and subsequent contraction, latency, constriction velocity, and dilation velocity were recorded using an electronic pupillometer. All pupil measurements were performed before and after pharmacologic dilation.
Results
In predilation pupillary measurements, we detected a significant decrease in maximum pupillary diameter by 0.50 ± 0.19 mm ( P = .011) and in the mean percentage of diameter reduction after stimulation (5.23 ± 2.42%, P = .035) in the tamsulosin group. Alfuzosin also induced a significant decrease in maximum pupillary diameter (0.49 ± 0.17 mm, P = .005). Constriction velocity was significantly reduced by 0.70 ± 0.20 m/s ( P = .001) in the tamsulosin group and by 0.54 ± 0.18 m/s ( P = .004) in the alfuzosin group. In terms of postdilation measurements, maximum and minimum pupil diameters were reduced significantly only in the tamsulosin group (by 1.09 ± 0.31 mm [ P = .001] and by 0.89 ± 0.36 mm [ P = .016], respectively).
Conclusions
We describe a reliable, accurate, and rapid method to acquire quantitative pupil measurements and identify the tendency for intraoperative floppy iris syndrome before cataract surgery after the use of alfuzosin and tamsulosin. This investigation also analyzed the similarities and differences induced by the 2 drugs in predilation and postdilation pupil dynamics, demonstrating that tamsulosin is more potent than alfuzosin in inducing intraoperative floppy iris syndrome.
Intraoperative floppy iris syndrome was first described by Chang and Campbell in 2005. This syndrome is characterized by a triad of intraoperative features: 1) a flaccid iris stroma that flutters and billows in response to ordinary intraocular fluid currents; 2) a tendency for the floppy iris stroma to prolapse toward the phaco and side-port incisions despite proper wound construction; and 3) progressive pupil constriction despite standard preoperative pharmacologic measures designed to prevent this. When all 3 features are present, intraoperative floppy iris syndrome is designated as complete (severe), but when even 1 feature is missing, intraoperative floppy iris syndrome is denoted as incomplete (mild/moderate). Without adequate pupil dilation, intraoperative floppy iris syndrome may reduce the surgical field and lead to complications, such as the risk of posterior capsular rupture, loss of vitreous, iris prolapse, iris stroma atrophy, capsulorrhexis tear, and anterior chamber hemorrhage. According to the most recent white paper by the American Society of Cataract and Refractive Surgery, there is a strong association between intraoperative floppy iris syndrome and oral administration of the α 1 -adrenergic receptor antagonist (α 1 -blocker) tamsulosin, a selective α 1A – and α 1D -adrenergic receptor antagonist, which is a commonly prescribed medication for the treatment of benign prostatic hyperplasia. Intraoperative floppy iris syndrome is 9 times more prevalent in male patients. It has been postulated that 40% to 90% of patients on tamsulosin develop intraoperative floppy iris syndrome. Tamsulosin has also been associated with a 2.3-fold increase in the postoperative cataract complication rate. Furthermore, other α-antagonists have been associated with intraoperative floppy iris syndrome, such as doxazosin, terazosin, alfuzosin, and labetalol, which is a β- and α 1 -blocker. Intraoperative floppy iris syndrome has also been observed in patients taking finasteride, mianserin, and antipsychotic agents. Chlorpromazine and donepezil may be added to the list of drugs that can cause floppy iris syndrome because of their α-receptor-blocking activities. However, a recent study reported that nonselective α-antagonists are unlikely to be associated with intraoperative floppy iris syndrome. In addition, although it can occur without the use of α 1 -adrenergic antagonists, no statistically significant association has been found between intraoperative floppy iris syndrome and other medications or disease.
In light of these findings, we performed a prospective investigation to study the pupil dynamics in patients taking 2 different types of α-antagonists, tamsulosin and alfuzosin, using the new hand-held portable NeurOptics pupillometer (Irvine, California, USA). The high rate of intraoperative complications, as well as possible postoperative limitations in the quality of patients’ vision, highlights the importance of identifying pupils with a high likelihood of developing intraoperative floppy iris syndrome prior to cataract surgery. In other studies, pupil measurements were made using a pupil gauge or an infrared but not a digital pupillometer, which has significant intra- and inter-observer variability. This variability limited the reliability of the values. These limitations are overcome by a digital, electronic pupillometer. To the best of our knowledge, this study is the first in the field using this instrument, which allows the reliable acquisition of quantitative pupil measurements and introduces a potent uniform standard for pupil assessment. Moreover, it allows the detailed assessment of pupil dynamics among patients taking α-blocker medication.
Methods
Patient/Study Population
Twenty-five control patients, 15 case patients who were treated with tamsulosin (duration, mean 2.60 ± 0.81 years, ranging from 0.5 to 10 years), and 22 patients who were treated with alfuzosin (duration, mean 3.64 ± 0.49 years, ranging from 0.5 to 10 years) were enrolled in our current study. This study was performed in the ophthalmology clinic of “Attikon” University Hospital and of “General Hospital of Nikaia” in Athens, Greece, between June 1, 2010 and February 20, 2011. All patients were referred to the urology clinic for benign prostatic hyperplasia and submitted to routine eye examinations in the ophthalmologic clinic.
Inclusion criteria were the current usage of tamsulosin or alfuzosin by case patients for at least 6 months. Pupil measurements were performed while the patients were taking tamsulosin. Women were excluded from this study. Pseudophakic patients were also excluded. Other exclusion criteria were previous ocular surgery, history of optic neuritis, or other neurologic disorders that could affect pupil dynamics (eg, Marcus Gunn pupil), pseudoexfoliation syndrome, uveitis-iritis, retinopathy of diabetes or other vascular diseases, age-related macular degeneration or other maculopathies, glaucoma, and any thrombotic disease. Patients were also excluded if they had taken any form of neuroleptic medication or used any eye drops other than artificial tears.
Twenty-five control patients were selected from all male patients attending the ophthalmology clinic. The inclusion criterion for the controls was age match to our study participants. Exclusion criteria were the same as those for the patients. Medication history of the patients and controls was recorded.
Pupillary Measurements
A standard pupil dilation regimen of 1 drop of tropicamide 0.5% and phenylephrine hydrochloride 10% was used 3 times over the course of a half hour (time points: 0 minutes, 10 minutes, 20 minutes) and the measurements were made at time points 10 minutes, 20 minutes and 30 minutes. Similarly with other neurophthalmic studies of the pupil, the first predilation measurement was made immediately before administration of the dilation drops, and the postdilation measurement was made 30 minutes later, in the same ambient lighting conditions.
The ForSite digital pupillometer (NeurOptics Inc, Irvine, California, USA) is a newly introduced pupillometer, which is a fully automated portable handheld device for monocular measurements.
The NeurOptics pupillometer incorporates a white-light flash emitter and an infrared digital video camera to record the changes in the responding pupil. The device emits a constant infrared light, the wavelength of which (850 nm) is beyond the normal range perceived by the human eye. To stimulate the pupil, it then emits a flash of white light of fixed intensity for a duration of 0.8 seconds. Simultaneously, an integrated video camera records the changes in pupil size at a speed of 40 frames per second. The device analyzes 124 images in each measurement sequence and provides detailed information regarding a number of pupil functions within 3 to 4 seconds. From this information, the following dynamic pupillary variables are calculated ( Table 1 ): maximum and minimum pupillary diameters (Max A and Min A, respectively, measured to 0.1 mm), the percentage change in diameter before and after constriction ([Max A – Min A]/Max A × 100), constriction latency, and the velocities of constriction and dilation. The results are displayed on an LCD screen with a graphical representation and numerical values. The device detects the largest pupil diameter of every image, and the software calculates the mean value of each pupil parameter and the standard deviation of the acquired images and automatically discards images of outliers.
| Pupillometer Measurement | Description |
|---|---|
| Maximum aperture (mm) | Pupil diameter in its resting state |
| Minimum aperture (mm) | Pupil size following contraction |
| Percentage change | Min A/Max A × 100 |
| Latency (ms) | Time from the light emission to first contraction |
| Constriction velocity (m/s) | Speed of pupil contraction |
| Dilation velocity (m/s) | Speed of pupil relaxation |
Statistical Methods
Statistical analysis was performed using Excel (Microsoft Corporation, Redmond, Washington, USA) and SPSS software (version 16; Statistical Package for Social Sciences, Chicago, Illinois, USA). The comparison of the mean data was performed with multiple comparisons. Continuous variables were described as the mean ± standard deviation (SD). A P value of < .05 was considered to be statistically significant.
Results
The pupillometer was robust and easy to operate, and all quantitative pupillometry measurements were reproducible. The predilation pupil measurement means are shown in Table 2 and revealed a significant difference between the control and tamsulosin groups as well as between the control and the alfuzosin groups. In addition, there was a statistically significant difference in postdilation pupil measurements between the control group and the α-blocker-treated groups ( Table 3 ). All of the measurements were performed in right and left eyes. These results showed that findings from both eyes were similar ( Tables 2 and 3 ).
| Parameter | Predilation | ||||||
|---|---|---|---|---|---|---|---|
| Right Eyes | Left Eyes | ||||||
| Mean ± SEM | Difference vs Control Group, Mean ± SEM | P Value | Mean ± SEM | Difference vs Control Group, Mean ± SEM | P Value | ||
| Maximum aperture (mm) | Control group | 3.53 ± 0.14 | 3.56 ± 0.14 | ||||
| Tamsulosin group | 3.03 ± 0.14 | −0.50 ± 0.19 | .011 | 2.94 ± 0.14 | −0.62 ± 0.20 | .003 | |
| Alfuzosin group | 3.04 ± 0.10 | −0.49 ± 0.17 | .005 | 3.08 ± 0.11 | −0.48 ± 0.18 | .010 | |
| Minimum aperture (mm) | Control group | 2.41 ± 0.07 | 2.42 ± 0.08 | ||||
| Tamsulosin group | 2.27 ± 0.11 | −0.14 ± 0.11 | .217 | 2.24 ± 0.13 | −0.18 ± 0.12 | .096 | |
| Alfuzosin group | 2.24 ± 0.06 | −0.17 ± 0.10 | .088 | 2.25 ± 0.05 | −0.17 ± 0.11 | .073 | |
| Percentage change | Control group | 30.16 ± 1.49 | 29.48 ± 1.71 | ||||
| Tamsulosin group | 24.93 ± 1.87 | −5.23 ± 2.42 | .035 | 23.67 ± 2.16 | −5.81 ± 2.74 | .038 | |
| Alfuzosin group | 25.95 ± 1.59 | −4.21 ± 2.17 | .057 | 26 ± 1.75 | −3.48 ± 2.45 | .161 | |
| Latency (ms) | Control group | 0.27 ± 0.01 | 0.26 ± 0.01 | ||||
| Tamsulosin group | 0.28 ± 0.01 | 0.01 ± 0.01 | .511 | 0.28 ± 0.01 | 0.02 ± 0.01 | .225 | |
| Alfuzosin group | 0.28 ± 0.01 | 0.01 ± 0.01 | .619 | 0.28 ± 0.01 | 0.02 ± 0.01 | .164 | |
| Constriction velocity (m/s) | Control group | 2.06 ± 0.14 | 2.05 ± 0.16 | ||||
| Tamsulosin group | 1.36 ± 0.12 | −0.70 ± 0.20 | .001 | 1.36 ± 0.15 | −0.68 ± 0.23 | .004 | |
| Alfuzosin group | 1.52 ± 0.12 | −0.54 ± 0.18 | .004 | 1.57 ± 0.14 | −0.48 ± 0.20 | .022 | |
| Dilation velocity (m/s) | Control group | 0.85 ± 0.05 | 0.85 ± 0.06 | ||||
| Tamsulosin group | 0.77 ± 0.05 | −0.09 ± 0.08 | .279 | 0.75 ± 0.05 | −0.10 ± 0.08 | .122 | |
| Alfuzosin group | 0.79 ± 0.06 | −0.07 ± 0.07 | .356 | 0.80 ± 0.05 | −0.05 ± 0.07 | .513 | |
| Parameter | Postdilation | ||||||
|---|---|---|---|---|---|---|---|
| Right Eyes | Left Eyes | ||||||
| Mean ± SEM | Difference vs Control Group, Mean ± SEM | P Value | Mean ± SEM | Difference vs Control Group, Mean ± SEM | P Value | ||
| Maximum aperture (mm) | Control group | 7.27 ± 0.17 | 7.42 ± 0.16 | ||||
| Tamsulosin group | 6.18 ± 0.29 | −1.09 ± 0.31 | .001 | 6.29 ± 0.30 | −1.13 ± 0.30 | .001 | |
| Alfuzosin group | 7.18 ± 0.19 | −0.09 ± 0.28 | .749 | 7.21 ± 0.15 | −0.19 ± 0.22 | .393 | |
| Minimum aperture (mm) | Control group | 7.04 ± 0.25 | 7.27 ± 0.20 | ||||
| Tamsulosin group | 6.14 ± 0.27 | −0.89 ± 0.36 | .016 | 6.25 ± 0.29 | −1.02 ± 0.33 | .006 | |
| Alfuzosin group | 7.04 ± 0.21 | 0.00 ± 0.32 | .990 | 6.91 ± 0.22 | −0.36 ± 0.30 | .291 | |
| Percentage change | Control group | 2.00 ± 0.50 | 1.88 ± 0.39 | ||||
| Tamsulosin group | 2.29 ± 0.80 | 0.29 ± 0.88 | .748 | 2.43 ± 0.89 | 0.55 ± 0.90 | .550 | |
| Alfuzosin group | 2.14 ± 0.49 | 0.14 ± 0.80 | .859 | 4.24 ± 2.22 | 2.36 ± 2.24 | .306 | |
| Latency (ms) | Control group | 0.28 ± 0.02 | 0.30 ± 0.04 | ||||
| Tamsulosin group | 0.34 ± 0.04 | 0.06 ± 0.05 | .125 | 0.37 ± 0.06 | 0.07 ± 0.07 | .390 | |
| Alfuzosin group | 0.32 ± 0.04 | 0.04 ± 0.04 | .244 | 0.29 ± 0.04 | −0.01 ± 0.20 | .708 | |
| Constriction velocity (m/s) | Control group | 0.24 ± 0.06 | 0.41 ± 0.22 | ||||
| Tamsulosin group | 0.27 ± 0.09 | 0.03 ± 0.52 | .950 | 0.27 ± 0.10 | −0.14 ± 0.24 | .597 | |
| Alfuzosin group | 0.74 ± 0.47 | 0.51 ± 0.47 | .288 | 2.39 ± 1.92 | 1.98 ± 1.93 | .315 | |
| Dilation velocity (m/s) | Control group | 0.13 ± 0.03 | 0.12 ± 0.04 | ||||
| Tamsulosin group | 0.14 ± 0.04 | 0.01 ± 0.72 | .991 | 0.13 ± 0.05 | 0.01 ± 0.06 | .815 | |
| Alfuzosin group | 0.85 ± 0.66 | 0.72 ± 0.65 | .274 | 1.06 ± 0.84 | 0.94 ± 0.84 | .273 | |
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