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ARTICLE
Intracameral mydriatics versus topical mydriatics in pupil dilation for phacoemulsification cataract surgery Amelia Lim Lay Suan, MD, M.Surg Ophthal, Jemaima Che Hamzah, MD, M.Surg Ophthal, PhD, Tan Soo Ken, MD, M.Med Ophthal, Vanessa Naseem Mansurali, MB BS, FRCS
Purpose: To evaluate the efficacy and safety of intracameral mydriatics (lidocaine 1.0% and phenylephrine 1.5%) versus topical mydriatics (phenylephrine 2.5% and tropicamide 1.0%) in pupil dilation for phacoemulsification surgery in Malaysians. Setting: Department of Ophthalmology, Penang General Hospital, Georgetown Penang, Malaysia.
Design: Prospective comparative case series. Method: Patients with immature cataract were randomized to the topical mydriatic group (topical group) or intracameral mydriatic group (intracameral group). Patients with small pupils and complicated cataracts were excluded. Pupil diameter changes were measured throughout the surgery. Additional pupil dilation maneuvers and complications were recorded.
A
dequate pupil dilation is important in any cataract surgery. Small pupils can compromise cataract surgery and increase the risk for intraoperative complications. Pupil dilation is usually achieved by the standard therapy of topical administration of anticholinergic or sympathomimetic agents. However, there are disadvantages to using topical mydriatics. Topical eyedrops have slow and poor penetration through the cornea, which delays the onset of pupil dilation.1,2 In addition, the topical administration of mydriatic agents has low bioavailability of mydriatics in the anterior chamber.3 One percent or less of instilled mydriatic agents is absorbed through the corneal route because of physiologic and anatomic barriers.4,5 Therefore, a higher concentration of topical mydriatics is needed to achieve adequate mydriasis that, because of significant systemic
Results: The study comprised 112 patients. There was no difference in mean pupil dilation between the intracameral group (4.86 mm G 0.74 [SD]) and the topical group (4.88 G 0.91 mm) (P Z .86). However, the mean pupil size before capsulorhexis in the topical group (7.23 G 1.08 mm) was significantly larger than in the intracameral group (6.40 G 0.80 mm) (P Z .01). The pupils in the intracameral group continued to dilate during surgery (0.44 G 0.62 mm), while those in the topical group constricted ( 0.41 G 1.04 mm) (P < .001). Three patients in the intracameral group and 6 in the topical group required additional maneuvers for pupil dilation (P Z .49). Each group had 1 complication (P Z 1.00).
Conclusions: Intracameral mydriatic agents dilated heavily pigmented pupils for phacoemulsification cataract surgery. However, in the early stages of surgery, pupil dilation was slower than with topical agents. J Cataract Refract Surg 2017; 43:1031–1035 Q 2017 ASCRS and ESCRS
absorption, can cause systemic toxicity such as acute pulmonary edema and hypertensive crisis. This commonly occurs in children6 and high-risk patients with uncontrolled hypertension or poor cardiac function.7,8 In addition, although topical mydriatics might achieve good pupil dilation at the initial stage of cataract surgery, their effect usually wears off during surgery.9 Pupil constriction during cataract surgery is a typical event in patients with intraoperative floppy-iris syndrome10 and those with diabetes mellitus (DM).11 Using intracameral mydriatics to dilate the pupil simplifies cataract surgery by reducing preoperative waiting time and thus increases the turnover rate of cataract surgery. The use of the intracameral dilating method also potentially decreases the risk for life-threatening systemic side effects because these agents are used at a lower dosage than topical mydriatic agents, which are absorbed
Submitted: November 20, 2016 | Final revision submitted: April 11, 2017 | Accepted: May 21, 2017 From the Ophthalmology Department (Lay Suan, Ken, Mansurali), Penang General Hospital, Georgetown Penang, and the Universiti Kebangsaan Malaysia Medical Centre (Hamzah), Kuala Lumpur, Malaysia. Corresponding author: Jemaima Che Hamzah, MD, M.Surg Ophthal, PhD, Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. E-mail: [email protected]. Q 2017 ASCRS and ESCRS Published by Elsevier Inc.
0886-3350/$ - see frontmatter http://dx.doi.org/10.1016/j.jcrs.2017.05.031
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systemically through the nasal mucosal and conjunctival tissues. In addition, compared with topical mydriatics, intracameral mydriatics reduce the need for frequent instillation. This could reduce the risk for dry eye, which can lead to a poor intraoperative view. The majority of Malaysians have heavily pigmented irides. However, to our knowledge, there is no study that shows the combination of intracameral phenylephrine 1.5% and intracameral lidocaine 1.0% is effective in producing pupil dilation for cataract surgery in Malaysians. PATIENTS AND METHODS This prospective randomized single-blinded trial evaluated patients scheduled for phacoemulsification cataract surgery. This study was approved by the Medical Research and Ethics Committee of Malaysia (Code: NMRR-12-1349-14527) and the Ethics Committee of the National University of Malaysia (Code: FF-2013-394) in accordance with the tenets of the Declaration of Helsinki. Patients were eligible if they were older than 18 years and able to provide informed consent. Patients with pupil abnormalities, narrow anterior chambers, previous intraocular surgery, past ocular trauma, ocular inflammation with posterior synechiae, pseudoexfoliation, complicated or dense cataracts, scheduled for combined surgery (eg, cataract and glaucoma), chronic miotic or a-blocker use or systemic comorbidities that were thought to affect pupil dilation (eg, DM and single eyed) were excluded. Study patients were randomized into the topical mydriatic group (topical group) or the intracameral mydriatic group (intracameral group). The topical group had the standard preoperative cataract pupil-dilating therapy comprising topical tropicamide 1.0%, and phenylephrine 2.5% at 15-minute intervals for 1 hour before the surgery. The intracameral group was given placebo topical eyedrops while waiting for surgery and received an intracameral injection of 0.2 mL preservative-free mixture of lidocaine 1.0% and phenylephrine 1.5% at the beginning of the surgery after a paracentesis was created. The preservative-free mixture of intracameral lidocaine 1.0% and phenylephrine 1.5% was prepared under sterile conditions in the operating room using preservative-free 0.3 mL phenylephrine 10.0% and 1.0 mL lidocaine 2.0%. A balanced salt solution (0.7 mL) was added to the solution to form a 2.0 mL mixture. The pH of the preservative-free mixture was 6.0. Topical anesthesia of proparacaine 5.0% eyedrops were given to all patients before the commencement of surgery. The surgeries were performed using a standard technique on an Infiniti phacoemulsification machine (Alcon Laboratories, Inc.) by the same surgeon (V.N.M.). A baseline horizontal pupil diameter was measured in all patients using a Castroviejo caliper (before any method of pupil dilation) under the same intensity of operating
microscope light. The horizontal pupil diameter was chosen because topical sympathomimetics dilate the horizontal iris dilator muscle later than the vertical iris dilator muscle, in particular at the 12 o’clock and 6 o’clock regions. A microscope (M822 F40/F20, Leica Microsystems GmbH) was set at 71% main light and 21% Ottoflex light (Leica Microsystems GmbH) (coaxial light set to visualize the eye’s red reflex during surgery) throughout the surgery and during pupil measurements. All pupil measurements were measured horizontally 3 times and then averaged. All patients were brought out of the operating recovery room for 1 hour of pupil dilation after the baseline horizontal pupil diameter was measured. They were then were brought in again for cataract surgery. The horizontal pupil diameter was measured again after 1 hour of topical pupil dilation in the topical group and after 60 seconds of injecting the intracameral mydriatics but before the injection of an ophthalmic viscosurgical device (OVD) in the intracameral group. The horizontal pupil diameter measurements were repeated before insertion of the intraocular lens (without OVD) and at the end of the surgery (after removal of the OVD) in both groups. Healon GV (sodium hyaluronate 1.4%) was used in all cases. The same phacoemulsification was used in all eyes. A clear corneal incision was created using a 2.75 mm microkeratome. Next, the vertical phaco-chop or divide-and-conquer technique was used according to the density of nucleus. A balanced salt irrigating solution with 1:100 000 adrenaline was used in both groups. The total surgical time was recorded. For cases in which pupil dilation was difficult, the types of additional maneuvers were recorded. The blood pressure and heart rate of all patients were recorded. Data were entered into a data-collection sheet and then transferred to SPSS software (version 22.0, International Business Machines Corp.). The pupil diameter was calculated and reported as the mean G SD. The independent t test was used to analyze the differences in mean pupil size, blood pressure, heart rate, and mean arterial pressure between the topical group and intracameral group. The t test was based on the assumption that the population was normally distributed. The Pearson chi-square test was used to analyze the differences in additional maneuvers used and local complications between the topical group and the intracameral group. A P value less than 0.05 was considered statistically significant.
RESULTS This study comprised 112 patients, with 56 patients in each group. Table 1 shows the patients’ demographics. All baseline parameters were comparable between the 2 groups. Table 2 shows the mean pupil diameter and surgical time. The difference in the mean increase in pupil dilation from baseline to the end of surgery between the intracameral
Table 1. Demographic characteristics of patients. Group Parameter
Intracameral Mydriatic
Sex Male Female Ethnicity Malay Chinese Indian Mean age (y) G SD CI Z confidence interval *Pearson chi-square test † Independent t test
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Topical Mydriatic
21 35
27 29
12 37 7 62.66 G 6.45
15 35 6 63.20 G 5.22
P Value
95% CI
.25*
d
.79*
d
.63†
2.73, 1.66
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Table 2. Mean pupil diameters and surgical time. Mean ± SD Parameter Pupil size (mm) Baseline Before capsulorhexis Before IOL implantation At end of surgery Dilated from baseline to end of surgery Surgical time (min)
95% CI of Difference
Intracameral Mydriatic Group
Topical Mydriatic Group
Mean Difference
1.98 G 0.33 6.40 G 0.80 6.80 G 0.69 6.84 G 0.80 4.86 G 0.74
1.94 G 0.29 7.23 G 1.08 6.96 G 0.89 6.82 G 0.95 4.88 G 0.91
0.04 0.83 0.15 0.02 0.03
24.11 G 8.97
23.48 G 10.14
0.63
P Value*
Lower
Upper
.45 .01 .31 .91 .86
0.07 1.19 0.45 0.31 0.34
0.16 0.47 0.14 0.35 0.28
.73
2.96
4.21
CI Z confidence interval; IOL Z intraocular lens *Independent t test
group and the topical group was not statistically significant (P Z .86; 95% confidence interval [CI] 0.34 to 0.28). Intracameral mydriatics did not cause significantly larger pupil dilation than topical mydriatics. However, there was a statistically significant difference in the mean pupil dilation size before capsulorhexis, which was higher in the topical group than in the intracameral group (P Z .01; 95% CI, 1.19 to 0.47). The pupils in the intracameral group continued to dilate throughout the surgery (mean 0.44 G 0.62 mm), while those in the topical group tended to constrict (mean 0.41 G 1.04 mm) (P ! .001). The mean surgical time in the intracameral group was slightly longer than in the topical group. However, there was no statistically significant difference between the 2 groups. Three patients in the intracameral group and 6 in the topical group required additional maneuvers to further dilate their pupils. Statistically, the use of additional methods to further dilate pupils was not significant in both groups (P Z .49). Table 3 shows the changes in blood pressure and heart rate between preoperatively and postoperatively. There was a statistically significant reduction in mean systolic blood pressure in the intracameral group from preoperatively and postoperatively and a statistically significant increase in the topical group. The difference was statistically significant (P Z .04; 95% CI, 12.66 to 0.23). The mean arterial pressure in both groups increased slightly from preoperatively to postoperatively. However, the difference was not statistically significant (P Z .51). One patient in each group developed intraoperative complications. The patient in the intracameral group had zonular dehiscence. The patient in the topical group
developed progressively anterior chamber shallowing that was thought to be caused by misdirection of fluid into the vitreous cavity, resulting in anterior displacement of the lens and iris diaphragm (posterior infusion syndrome). The difference in intraoperative complications between groups was not statistically significant (P Z 1.00). DISCUSSION Topical mydriatic agents have been routinely used to dilate pupils preoperatively in cataract surgery. However, the use of benzalkonium chloride as a preservative in topical eyedrops has led to side effects, mainly on the cornea (eg, punctate epithelial erosion causing poor intraoperative surgical view). In addition, topical mydriatic agents might cause elevated blood pressure secondary to systemic absorption via mucosa and episcleral blood vessels. Therefore, alternative methods of pupil dilation have been assessed with the goal of decreasing the risk for unwanted local and systemic side effects. Many clinical trials9,12–16 compared the effectiveness of topical mydriatics with that of intracameral lidocaine 1.0% alone or intracameral lidocaine 1.0% in combination with other mydriatic agents such as cyclopentolate 0.1% and phenylephrine 1.5%. These studies found that the use intracameral mydriatics alone produced prompt pupil dilation intraoperatively without the previous use of topical mydriatics. Intracameral lidocaine 1.0% is likely to induce mydriasis by causing relaxation of the iris sphincter. Apart from that, its anesthetic effect helps enhance the patient’s comfort during the surgical procedure. The clinical trials9,12–16 found that intracameral mydriatics produced adequate pupil dilation during cataract surgery.
Table 3. Blood pressure and heart rate changes from preoperatively to postoperatively. Mean Change ± SD Parameter Systolic blood pressure (mm Hg) Diastolic blood pressure (mmHg) Mean arterial pressure (mm Hg) Heart rate (pulse per min)
Intracameral Mydriatic Group 3.00 G 16.15 2.23 G 8.87 0.49 G 10.12 7.75 G 19.16
Topical Mydriatic Group 3.50 G 17.32 0.88 G 9.59 1.75 G 10.23 6.09 G 17.88
95% CI of Difference Mean Difference 6.50 1.36 1.26 1.66
P Value* .04 .44 .51 .64
Lower 12.66 2.10 5.07 5.28
Upper 0.23 4.82 2.55 8.60
CI Z confidence interval *Independent t test
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The caveat from these studies was that the patients predominantly had lightly pigmented irides. The potential advantages of intracameral mydriatics are multiple. First, omission of preoperative dilating eyedrops will ease the burden on the hospital staff. Moreover, their use in cataract surgery prevents the corneal side effects of intensive preoperative topical mydriatic agents. In addition, surgery can be scheduled using a staggered system to reduce the waiting time for patients. A study by Cionni et al.14 found that intracameral lidocaine 1.0% was effective in attaining good pupil dilation without the use of topical mydriatics preoperatively. The mydriatic effect of intracameral mydriatics did not wear off during the surgery, and the pupils were further dilated at the end of surgery. Lee et al.15 evaluated the use of intracameral lidocaine 1.0% to dilate the pupil in glaucoma filtering surgery intraoperatively and showed that intracameral lidocaine 1.0% can be used as a dilating agent in undilated eyes. A study by Nikeghbali et al.16 found that both intracameral lidocaine 1.0% and topical groups (cyclopentolate 1.0% and phenylephrine 5.0%) achieved significant pupil dilation in cataract surgery. In contrast to our findings, there was greater pupil dilation in the intracameral mydriatic group than in the topical group. We found greater pupil dilation in the topical group than in the intracameral group in the early stage of cataract surgery, just before creation of the capsulorhexis. Lundberg and Behndig9 showed that the pupil dilation in eyes that received intracameral mydriatics (cyclopentolate 1.0%, phenylephrine 1.5%, and lidocaine 1.0%) could achieve 95% of their maximum size after 20 seconds of injection. They also found that use of intracameral mydriatics further dilated the pupil intraoperatively, whereas the pupil diameter in the topical mydriatic group (cyclopentolate 1.0% and phenylephrine 10.0%) was smaller at the end of surgery. The mean pupil size in the intracameral group was smaller than in the topical group at the initial stage of cataract surgery. This is similar to our topical group, which had greater pupil dilation than the intracameral group before capsulorhexis creation. Our study also found that the pupil in the intracameral group continued to dilate throughout the surgery, while the topical group had a reduction in pupil size toward the end of surgery. Malaysia is a multiracial country consisting of 3 main ethnic groups; that is, Malays, Chinese, and Indians. They have heavily pigmented irides, especially the Indian population, and it has been thought that pupil dilation in these eyes is slower and that extra methods might be needed to further dilate the pupils. Lee et al.15 found that at the early stage of pupil dilation, the pupil diameter in eyes with blue irides was greater than in eyes brown irides. However, they did not find a difference in pupil size after 5 minutes of dilation. Intracameral mydriatic agents are useful in augmenting pupil dilation as opposed to their use as a sole method for pupil dilation. Topical mydriatic agents that have adrenergic stimulation can cause unwanted systemic side effects, such as raised blood pressure and tachycardia. Intravenous phenylephrine 100 mcg per bolus dose is often given during Volume 43 Issue 8 August 2017
resuscitation to manage hypotension. A bottle of topical phenylephrine has a higher concentration of phenylephrine to provide adequate bioavailability of phenylephrine in the anterior chamber for pupil dilation. The 2 commercially available concentrations of topical phenylephrine are 2.5% and 10.0%. A drop of topical phenylephrine 2.5% contains 1250 mcg of phenylephrine, while a drop of phenylephrine 10.0% has 5000 mcg of phenylephrine. These calculations are based on a drop size of 50 mL. Compared with a rescue dose of intravenous phenylephrine for hypotension, there is 12.5 times and 50.0 times higher dosage of topical phenylephrine 2.5% and 10.0%, respectively. Repeated drops of high-concentration topical phenylephrine can cause a rise in blood pressure. Severely increased blood pressure can lead to life-threatening events, such as a hypertensive crisis, acute pulmonary edema, myocardial infarction, or cerebrovascular accident. This might unnecessarily expose patients having an elective procedure (cataract surgery) to a life-threatening risk. We found that there was statistically significant difference in terms of preoperative and postoperative systolic blood pressure changes in both groups. The intracameral group had a reduction of systolic blood pressure, while the topical group had an increase in systolic blood pressure. However, there was minimal increase in mean arterial pressure and heart rate postoperatively. Both mean arterial pressure and heart rate were not statistically different between both groups. Intracameral mydriatics was shown to be a safe alternative for pupil dilation in high-risk patients, especially patients with cardiovascular risk factors.9 Lundberg and Behndig9 found that a slight increase in mean arterial pressure was seen in both groups postoperatively. However, the minimally raised postoperative mean arterial pressure did not differ significantly from the preoperative mean arterial pressure. A decline in heart rate was also seen in both groups, but only the topical group had a statistically significant deceleration of heart rate. Systolic blood pressure is a better predictor of cardiovascular risk.17 Studies18,19 show that systolic blood pressure should be the primary target of hypertension management. High blood pressure increases the pulse pressure, which is a potential independent risk factor for cardiovascular disease. In our study, there was a reduction in systolic blood pressure in the intracameral group, suggesting that intracameral mydriatics are safe for patients with cardiovascular risks. Adequate pupil dilation for cataract surgery reduces the risk for intraoperative complications such as posterior capsule tear, iris trauma, bleeding, and zonular fiber dialysis with or without vitreous loss. Despite studies reporting intracameral mydriatic agents produced adequate pupil dilation for phacoemulsification,9,12–16 additional maneuvers were required to further dilate the pupils in both groups in our study. This agrees with findings in a study by Lundberg and Behndig9 in which mechanical pupil dilation was required in both groups. Conversely, in a study by Nikeghbali et al.16 patients in the intracameral group did not require additional methods to maintain pupil dilation compared with the topical group.
INTRACAMERAL VS TOPICAL MYDRIATICS FOR PUPIL DILATION
In our study, zonular dehiscence occurred intraoperatively in 1 patient in the intracameral group. One patient in the topical group developed progressive shallowing of the anterior chamber intraoperatively. The complication was likely the result of misdirection of fluid into the vitreous cavity, causing anterior displacement of the lens and iris diaphragm (posterior infusion syndrome). Both complications could have been the result of underlying preexisting weak zonular fibers rather than poor pupil dilation. A limitation of this study was that Castroviejo calipers were used to measure the pupils. The optical properties of the cornea can magnify and anteriorly displace the image. Therefore, the pupil size measurements using these calipers might not represent the actual pupil size. To dilate the eyes of 200 patients, a box of minims phenylephrine hydrochloride 10.0% and 40 bottles of lidocaine hydrochloride blood pressure 1.0% are needed. These medications cost approximately US $16.00 and US $11.00, respectively. Thus, the total price for an intracameral mydriatic mixture to dilate the eyes of 200 patients is approximately US $27.00. Meanwhile, a 5 mL bottle of tropicamide 1.0% and phenylephrine 2.5% can be used to dilate the eyes of 25 patients and costs approximately US $2.00 and US $2.40, respectively. Therefore, approximately 8 bottles of each tropicamide and phenylephrine eyedrops are needed to dilate the eyes of 200 patients, with a cost approximating US $35.20. These figures show that intracameral mydriatics are more cost effective than topical mydriatics. However, the price of the medications varies from country to country. In conclusion, our study found that intracameral mydriatic agents were comparable to topical agents in dilating pupils for cataract surgery, even in Asian eyes. However, pupil dilation was slower in the intracameral group than in the topical group in the early stages of surgery. Further study to determine the cost effectiveness of these agents in cataract surgery is required.
2. 3.
4.
5.
6. 7.
8. 9. 10. 11.
12.
13.
14. 15.
16.
17.
WHAT WAS KNOWN
18.
Intracameral mydriatics are effective in dilating pupils in lightly pigmented eyes.
WHAT THIS PAPER ADDS Intracameral mydriatic agents were as effective as topical mydriatics in dilating heavily pigmented pupils for cataract surgery in Malaysian patients. The effect of pupil dilation increased toward the end of surgery in the intracameral group but decreased in the topical group. Pupil dilation was slower in the intracameral group than in the topical group in the early stages of phacoemulsification. Intracameral mydriatic agents might be useful to augment pupil dilation as opposed to their use as a sole dilating method.
19.
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Tocicol 1998; 82:19–22. Available at: http://onlinelibrary.wiley.com/doi /10.1111/j.1600-0773.1998.tb01392.x/pdf. Accessed June 9, 2017 Levine L. Effective degree of mydriasis with phenylephrine and tropicamide. Am J Optom Physiol Opt 1976; 53:774–785 Nicholson F, Clark KL, Brecker SJD, Smith SA. A pharmacological method for measuring the penetration of topical mydriatics in man. [letter]. Br J Clin Pharmacol 1982; 14:468–469. Available at: http://onlinelibrary.wiley.com /doi/10.1111/j.1365-2125.1982.tb02014.x/epdf. Accessed June 7, 2017 Saettone MF. Progress and problems in ophthalmic drug delivery. Business Briefing: Pharmatech 2002; 167–171. Available at: http://aciont.com/pdf /SaettoneOcularDrugDeliveryArticle.pdf. Accessed June 7, 2017 Patel PB, Shastri DH, Shelat PK, Shukla AK. Ophthalmic drug delivery system: challenges and approaches. Systemic Rev Pharm 2010; 1:113–120. Available at: http://www.sysrevpharm.org/sites/default/files/1-2_0.pdf. Accessed June 7, 2017 Claudia G. Systemic toxicity with topical ophthalmic medications in children. Paediatr Perinat Drug Ther 2006; 7:23–29 Kalyanaraman M, Carpenter RL, McGlew MJ, Guertin SR. Cardiopulmonary compromise after use of topical or submucosal a-agonists: possible added complication by the use of b-blocker therapy. Otolaryngol Head Neck Surg 1997; 117:56–61. Available at: http://journals.sagepub.com /doi/pdf/10.1016/S0194-59989770207-9. Accessed June 7, 2017 Rengstorff RH, Doughty CB. Mydriatic and cycloplegic drugs: a review of ocular and systemic complications. Am J Optom Physiol Opt 1982; 59:162–177 Lundberg B, Behndig A. Intracameral mydriatics in phacoemulsification cataract surgery. J Cataract Refract Surg 2003; 29:2366–2371 Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 2005; 31:664–673 €m C. Cataract surgery and pupil size in patients with diaZaczek A, Zetterstro betes mellitus. Acta Ophthalmol Scand 1997; 75:429–432. Available at: http://www3.interscience.wiley.com/cgi-bin/fulltext/122407159/PDFSTART. Accessed June 7, 2017 C, Gallagher M, Thomson S. Safety of intraSoong T, Soultanidis M, Claoue cameral mydriasis in phacoemulsification cataract surgery. [letter]. J Cataract Refract Surg 2006; 32:375–376 Behndig A, Eriksson A. Evaluation of surgical performance with intracameral mydriatics in phacoemulsification surgery. Acta Ophthalmol Scand 2004; 82:144–147. Available at: http://www3.interscience.wiley.com/cgi-bin /fulltext/118808583/PDFSTART. Accessed June 7, 2017 Cionni RJ, Barros MG, Kaufman AH, Osher RH. Cataract surgery without preoperative eyedrops. J Cataract Refract Surg 2003; 29:2281–2283 Lee JJ, Moster MR, Henderer JD, Membreno JH. Pupil dilatation with intracameral 1% lidocaine during glaucoma filtering surgery. Am J Ophthalmol 2003; 136:201–203 Nikeghbali A, Falavarjani KG, Kheirkhah A. Pupil dilation with intracameral lidocaine during phacoemulsification: benefits for the patient and surgeon. Indian J Ophthalmol 2008; 56:63–64. Available at: http://www.ncbi.nlm.nih.gov /pmc/articles/PMC2636064/?reportZprintable. Accessed June 7, 2017 Strandberg TE, Pitkala K. What is the most important component of blood pressure: systolic, diastolic or pulse pressure? Curr Opin Nephrol Hypertens 2003; 12:293–297 Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham Heart Study. Circulation 1999; 100:354–360. Available at: http://circ.aha journals.org/content/100/4/354.long. Accessed June 7, 2017 ~es JB, Menezes PPO, Almeida de Sousa JM, Hermann JLV, Guimara Carvalho ACC. Evaluation of systolic, diastolic and pulse pressure as risk factors for severe coronary arteriosclerotic disease in women with unstable angina non-ST-elevation acute myocardial infarction. Arq Bras Cardiol 2004; 82:430–433. Available at: http://www.scielo.br/pdf/abc/v82n5 /en_20275.pdf. Accessed June 7, 2017
Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned.
First author: Amelia Lim Lay Suan, MD, M.Surg Ophthal
REFERENCES
Ophthalmology Department, Penang General Hospital, Georgetown Penang, Malaysia
1. Haaga M, Kaila T, Salminen L, Ylitalo P. Systemic and ocular absorption and antagonist activity of topically applied cyclopentolate in man. Pharmacol
Volume 43 Issue 8 August 2017
ARTICLE
Intracameral mydriatics versus topical mydriatics in pupil dilation for phacoemulsification cataract surgery Amelia Lim Lay Suan, MD, M.Surg Ophthal, Jemaima Che Hamzah, MD, M.Surg Ophthal, PhD, Tan Soo Ken, MD, M.Med Ophthal, Vanessa Naseem Mansurali, MB BS, FRCS
Purpose: To evaluate the efficacy and safety of intracameral mydriatics (lidocaine 1.0% and phenylephrine 1.5%) versus topical mydriatics (phenylephrine 2.5% and tropicamide 1.0%) in pupil dilation for phacoemulsification surgery in Malaysians. Setting: Department of Ophthalmology, Penang General Hospital, Georgetown Penang, Malaysia.
Design: Prospective comparative case series. Method: Patients with immature cataract were randomized to the topical mydriatic group (topical group) or intracameral mydriatic group (intracameral group). Patients with small pupils and complicated cataracts were excluded. Pupil diameter changes were measured throughout the surgery. Additional pupil dilation maneuvers and complications were recorded.
A
dequate pupil dilation is important in any cataract surgery. Small pupils can compromise cataract surgery and increase the risk for intraoperative complications. Pupil dilation is usually achieved by the standard therapy of topical administration of anticholinergic or sympathomimetic agents. However, there are disadvantages to using topical mydriatics. Topical eyedrops have slow and poor penetration through the cornea, which delays the onset of pupil dilation.1,2 In addition, the topical administration of mydriatic agents has low bioavailability of mydriatics in the anterior chamber.3 One percent or less of instilled mydriatic agents is absorbed through the corneal route because of physiologic and anatomic barriers.4,5 Therefore, a higher concentration of topical mydriatics is needed to achieve adequate mydriasis that, because of significant systemic
Results: The study comprised 112 patients. There was no difference in mean pupil dilation between the intracameral group (4.86 mm G 0.74 [SD]) and the topical group (4.88 G 0.91 mm) (P Z .86). However, the mean pupil size before capsulorhexis in the topical group (7.23 G 1.08 mm) was significantly larger than in the intracameral group (6.40 G 0.80 mm) (P Z .01). The pupils in the intracameral group continued to dilate during surgery (0.44 G 0.62 mm), while those in the topical group constricted ( 0.41 G 1.04 mm) (P < .001). Three patients in the intracameral group and 6 in the topical group required additional maneuvers for pupil dilation (P Z .49). Each group had 1 complication (P Z 1.00).
Conclusions: Intracameral mydriatic agents dilated heavily pigmented pupils for phacoemulsification cataract surgery. However, in the early stages of surgery, pupil dilation was slower than with topical agents. J Cataract Refract Surg 2017; 43:1031–1035 Q 2017 ASCRS and ESCRS
absorption, can cause systemic toxicity such as acute pulmonary edema and hypertensive crisis. This commonly occurs in children6 and high-risk patients with uncontrolled hypertension or poor cardiac function.7,8 In addition, although topical mydriatics might achieve good pupil dilation at the initial stage of cataract surgery, their effect usually wears off during surgery.9 Pupil constriction during cataract surgery is a typical event in patients with intraoperative floppy-iris syndrome10 and those with diabetes mellitus (DM).11 Using intracameral mydriatics to dilate the pupil simplifies cataract surgery by reducing preoperative waiting time and thus increases the turnover rate of cataract surgery. The use of the intracameral dilating method also potentially decreases the risk for life-threatening systemic side effects because these agents are used at a lower dosage than topical mydriatic agents, which are absorbed
Submitted: November 20, 2016 | Final revision submitted: April 11, 2017 | Accepted: May 21, 2017 From the Ophthalmology Department (Lay Suan, Ken, Mansurali), Penang General Hospital, Georgetown Penang, and the Universiti Kebangsaan Malaysia Medical Centre (Hamzah), Kuala Lumpur, Malaysia. Corresponding author: Jemaima Che Hamzah, MD, M.Surg Ophthal, PhD, Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. E-mail: [email protected]. Q 2017 ASCRS and ESCRS Published by Elsevier Inc.
0886-3350/$ - see frontmatter http://dx.doi.org/10.1016/j.jcrs.2017.05.031
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systemically through the nasal mucosal and conjunctival tissues. In addition, compared with topical mydriatics, intracameral mydriatics reduce the need for frequent instillation. This could reduce the risk for dry eye, which can lead to a poor intraoperative view. The majority of Malaysians have heavily pigmented irides. However, to our knowledge, there is no study that shows the combination of intracameral phenylephrine 1.5% and intracameral lidocaine 1.0% is effective in producing pupil dilation for cataract surgery in Malaysians. PATIENTS AND METHODS This prospective randomized single-blinded trial evaluated patients scheduled for phacoemulsification cataract surgery. This study was approved by the Medical Research and Ethics Committee of Malaysia (Code: NMRR-12-1349-14527) and the Ethics Committee of the National University of Malaysia (Code: FF-2013-394) in accordance with the tenets of the Declaration of Helsinki. Patients were eligible if they were older than 18 years and able to provide informed consent. Patients with pupil abnormalities, narrow anterior chambers, previous intraocular surgery, past ocular trauma, ocular inflammation with posterior synechiae, pseudoexfoliation, complicated or dense cataracts, scheduled for combined surgery (eg, cataract and glaucoma), chronic miotic or a-blocker use or systemic comorbidities that were thought to affect pupil dilation (eg, DM and single eyed) were excluded. Study patients were randomized into the topical mydriatic group (topical group) or the intracameral mydriatic group (intracameral group). The topical group had the standard preoperative cataract pupil-dilating therapy comprising topical tropicamide 1.0%, and phenylephrine 2.5% at 15-minute intervals for 1 hour before the surgery. The intracameral group was given placebo topical eyedrops while waiting for surgery and received an intracameral injection of 0.2 mL preservative-free mixture of lidocaine 1.0% and phenylephrine 1.5% at the beginning of the surgery after a paracentesis was created. The preservative-free mixture of intracameral lidocaine 1.0% and phenylephrine 1.5% was prepared under sterile conditions in the operating room using preservative-free 0.3 mL phenylephrine 10.0% and 1.0 mL lidocaine 2.0%. A balanced salt solution (0.7 mL) was added to the solution to form a 2.0 mL mixture. The pH of the preservative-free mixture was 6.0. Topical anesthesia of proparacaine 5.0% eyedrops were given to all patients before the commencement of surgery. The surgeries were performed using a standard technique on an Infiniti phacoemulsification machine (Alcon Laboratories, Inc.) by the same surgeon (V.N.M.). A baseline horizontal pupil diameter was measured in all patients using a Castroviejo caliper (before any method of pupil dilation) under the same intensity of operating
microscope light. The horizontal pupil diameter was chosen because topical sympathomimetics dilate the horizontal iris dilator muscle later than the vertical iris dilator muscle, in particular at the 12 o’clock and 6 o’clock regions. A microscope (M822 F40/F20, Leica Microsystems GmbH) was set at 71% main light and 21% Ottoflex light (Leica Microsystems GmbH) (coaxial light set to visualize the eye’s red reflex during surgery) throughout the surgery and during pupil measurements. All pupil measurements were measured horizontally 3 times and then averaged. All patients were brought out of the operating recovery room for 1 hour of pupil dilation after the baseline horizontal pupil diameter was measured. They were then were brought in again for cataract surgery. The horizontal pupil diameter was measured again after 1 hour of topical pupil dilation in the topical group and after 60 seconds of injecting the intracameral mydriatics but before the injection of an ophthalmic viscosurgical device (OVD) in the intracameral group. The horizontal pupil diameter measurements were repeated before insertion of the intraocular lens (without OVD) and at the end of the surgery (after removal of the OVD) in both groups. Healon GV (sodium hyaluronate 1.4%) was used in all cases. The same phacoemulsification was used in all eyes. A clear corneal incision was created using a 2.75 mm microkeratome. Next, the vertical phaco-chop or divide-and-conquer technique was used according to the density of nucleus. A balanced salt irrigating solution with 1:100 000 adrenaline was used in both groups. The total surgical time was recorded. For cases in which pupil dilation was difficult, the types of additional maneuvers were recorded. The blood pressure and heart rate of all patients were recorded. Data were entered into a data-collection sheet and then transferred to SPSS software (version 22.0, International Business Machines Corp.). The pupil diameter was calculated and reported as the mean G SD. The independent t test was used to analyze the differences in mean pupil size, blood pressure, heart rate, and mean arterial pressure between the topical group and intracameral group. The t test was based on the assumption that the population was normally distributed. The Pearson chi-square test was used to analyze the differences in additional maneuvers used and local complications between the topical group and the intracameral group. A P value less than 0.05 was considered statistically significant.
RESULTS This study comprised 112 patients, with 56 patients in each group. Table 1 shows the patients’ demographics. All baseline parameters were comparable between the 2 groups. Table 2 shows the mean pupil diameter and surgical time. The difference in the mean increase in pupil dilation from baseline to the end of surgery between the intracameral
Table 1. Demographic characteristics of patients. Group Parameter
Intracameral Mydriatic
Sex Male Female Ethnicity Malay Chinese Indian Mean age (y) G SD CI Z confidence interval *Pearson chi-square test † Independent t test
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Topical Mydriatic
21 35
27 29
12 37 7 62.66 G 6.45
15 35 6 63.20 G 5.22
P Value
95% CI
.25*
d
.79*
d
.63†
2.73, 1.66
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Table 2. Mean pupil diameters and surgical time. Mean ± SD Parameter Pupil size (mm) Baseline Before capsulorhexis Before IOL implantation At end of surgery Dilated from baseline to end of surgery Surgical time (min)
95% CI of Difference
Intracameral Mydriatic Group
Topical Mydriatic Group
Mean Difference
1.98 G 0.33 6.40 G 0.80 6.80 G 0.69 6.84 G 0.80 4.86 G 0.74
1.94 G 0.29 7.23 G 1.08 6.96 G 0.89 6.82 G 0.95 4.88 G 0.91
0.04 0.83 0.15 0.02 0.03
24.11 G 8.97
23.48 G 10.14
0.63
P Value*
Lower
Upper
.45 .01 .31 .91 .86
0.07 1.19 0.45 0.31 0.34
0.16 0.47 0.14 0.35 0.28
.73
2.96
4.21
CI Z confidence interval; IOL Z intraocular lens *Independent t test
group and the topical group was not statistically significant (P Z .86; 95% confidence interval [CI] 0.34 to 0.28). Intracameral mydriatics did not cause significantly larger pupil dilation than topical mydriatics. However, there was a statistically significant difference in the mean pupil dilation size before capsulorhexis, which was higher in the topical group than in the intracameral group (P Z .01; 95% CI, 1.19 to 0.47). The pupils in the intracameral group continued to dilate throughout the surgery (mean 0.44 G 0.62 mm), while those in the topical group tended to constrict (mean 0.41 G 1.04 mm) (P ! .001). The mean surgical time in the intracameral group was slightly longer than in the topical group. However, there was no statistically significant difference between the 2 groups. Three patients in the intracameral group and 6 in the topical group required additional maneuvers to further dilate their pupils. Statistically, the use of additional methods to further dilate pupils was not significant in both groups (P Z .49). Table 3 shows the changes in blood pressure and heart rate between preoperatively and postoperatively. There was a statistically significant reduction in mean systolic blood pressure in the intracameral group from preoperatively and postoperatively and a statistically significant increase in the topical group. The difference was statistically significant (P Z .04; 95% CI, 12.66 to 0.23). The mean arterial pressure in both groups increased slightly from preoperatively to postoperatively. However, the difference was not statistically significant (P Z .51). One patient in each group developed intraoperative complications. The patient in the intracameral group had zonular dehiscence. The patient in the topical group
developed progressively anterior chamber shallowing that was thought to be caused by misdirection of fluid into the vitreous cavity, resulting in anterior displacement of the lens and iris diaphragm (posterior infusion syndrome). The difference in intraoperative complications between groups was not statistically significant (P Z 1.00). DISCUSSION Topical mydriatic agents have been routinely used to dilate pupils preoperatively in cataract surgery. However, the use of benzalkonium chloride as a preservative in topical eyedrops has led to side effects, mainly on the cornea (eg, punctate epithelial erosion causing poor intraoperative surgical view). In addition, topical mydriatic agents might cause elevated blood pressure secondary to systemic absorption via mucosa and episcleral blood vessels. Therefore, alternative methods of pupil dilation have been assessed with the goal of decreasing the risk for unwanted local and systemic side effects. Many clinical trials9,12–16 compared the effectiveness of topical mydriatics with that of intracameral lidocaine 1.0% alone or intracameral lidocaine 1.0% in combination with other mydriatic agents such as cyclopentolate 0.1% and phenylephrine 1.5%. These studies found that the use intracameral mydriatics alone produced prompt pupil dilation intraoperatively without the previous use of topical mydriatics. Intracameral lidocaine 1.0% is likely to induce mydriasis by causing relaxation of the iris sphincter. Apart from that, its anesthetic effect helps enhance the patient’s comfort during the surgical procedure. The clinical trials9,12–16 found that intracameral mydriatics produced adequate pupil dilation during cataract surgery.
Table 3. Blood pressure and heart rate changes from preoperatively to postoperatively. Mean Change ± SD Parameter Systolic blood pressure (mm Hg) Diastolic blood pressure (mmHg) Mean arterial pressure (mm Hg) Heart rate (pulse per min)
Intracameral Mydriatic Group 3.00 G 16.15 2.23 G 8.87 0.49 G 10.12 7.75 G 19.16
Topical Mydriatic Group 3.50 G 17.32 0.88 G 9.59 1.75 G 10.23 6.09 G 17.88
95% CI of Difference Mean Difference 6.50 1.36 1.26 1.66
P Value* .04 .44 .51 .64
Lower 12.66 2.10 5.07 5.28
Upper 0.23 4.82 2.55 8.60
CI Z confidence interval *Independent t test
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The caveat from these studies was that the patients predominantly had lightly pigmented irides. The potential advantages of intracameral mydriatics are multiple. First, omission of preoperative dilating eyedrops will ease the burden on the hospital staff. Moreover, their use in cataract surgery prevents the corneal side effects of intensive preoperative topical mydriatic agents. In addition, surgery can be scheduled using a staggered system to reduce the waiting time for patients. A study by Cionni et al.14 found that intracameral lidocaine 1.0% was effective in attaining good pupil dilation without the use of topical mydriatics preoperatively. The mydriatic effect of intracameral mydriatics did not wear off during the surgery, and the pupils were further dilated at the end of surgery. Lee et al.15 evaluated the use of intracameral lidocaine 1.0% to dilate the pupil in glaucoma filtering surgery intraoperatively and showed that intracameral lidocaine 1.0% can be used as a dilating agent in undilated eyes. A study by Nikeghbali et al.16 found that both intracameral lidocaine 1.0% and topical groups (cyclopentolate 1.0% and phenylephrine 5.0%) achieved significant pupil dilation in cataract surgery. In contrast to our findings, there was greater pupil dilation in the intracameral mydriatic group than in the topical group. We found greater pupil dilation in the topical group than in the intracameral group in the early stage of cataract surgery, just before creation of the capsulorhexis. Lundberg and Behndig9 showed that the pupil dilation in eyes that received intracameral mydriatics (cyclopentolate 1.0%, phenylephrine 1.5%, and lidocaine 1.0%) could achieve 95% of their maximum size after 20 seconds of injection. They also found that use of intracameral mydriatics further dilated the pupil intraoperatively, whereas the pupil diameter in the topical mydriatic group (cyclopentolate 1.0% and phenylephrine 10.0%) was smaller at the end of surgery. The mean pupil size in the intracameral group was smaller than in the topical group at the initial stage of cataract surgery. This is similar to our topical group, which had greater pupil dilation than the intracameral group before capsulorhexis creation. Our study also found that the pupil in the intracameral group continued to dilate throughout the surgery, while the topical group had a reduction in pupil size toward the end of surgery. Malaysia is a multiracial country consisting of 3 main ethnic groups; that is, Malays, Chinese, and Indians. They have heavily pigmented irides, especially the Indian population, and it has been thought that pupil dilation in these eyes is slower and that extra methods might be needed to further dilate the pupils. Lee et al.15 found that at the early stage of pupil dilation, the pupil diameter in eyes with blue irides was greater than in eyes brown irides. However, they did not find a difference in pupil size after 5 minutes of dilation. Intracameral mydriatic agents are useful in augmenting pupil dilation as opposed to their use as a sole method for pupil dilation. Topical mydriatic agents that have adrenergic stimulation can cause unwanted systemic side effects, such as raised blood pressure and tachycardia. Intravenous phenylephrine 100 mcg per bolus dose is often given during Volume 43 Issue 8 August 2017
resuscitation to manage hypotension. A bottle of topical phenylephrine has a higher concentration of phenylephrine to provide adequate bioavailability of phenylephrine in the anterior chamber for pupil dilation. The 2 commercially available concentrations of topical phenylephrine are 2.5% and 10.0%. A drop of topical phenylephrine 2.5% contains 1250 mcg of phenylephrine, while a drop of phenylephrine 10.0% has 5000 mcg of phenylephrine. These calculations are based on a drop size of 50 mL. Compared with a rescue dose of intravenous phenylephrine for hypotension, there is 12.5 times and 50.0 times higher dosage of topical phenylephrine 2.5% and 10.0%, respectively. Repeated drops of high-concentration topical phenylephrine can cause a rise in blood pressure. Severely increased blood pressure can lead to life-threatening events, such as a hypertensive crisis, acute pulmonary edema, myocardial infarction, or cerebrovascular accident. This might unnecessarily expose patients having an elective procedure (cataract surgery) to a life-threatening risk. We found that there was statistically significant difference in terms of preoperative and postoperative systolic blood pressure changes in both groups. The intracameral group had a reduction of systolic blood pressure, while the topical group had an increase in systolic blood pressure. However, there was minimal increase in mean arterial pressure and heart rate postoperatively. Both mean arterial pressure and heart rate were not statistically different between both groups. Intracameral mydriatics was shown to be a safe alternative for pupil dilation in high-risk patients, especially patients with cardiovascular risk factors.9 Lundberg and Behndig9 found that a slight increase in mean arterial pressure was seen in both groups postoperatively. However, the minimally raised postoperative mean arterial pressure did not differ significantly from the preoperative mean arterial pressure. A decline in heart rate was also seen in both groups, but only the topical group had a statistically significant deceleration of heart rate. Systolic blood pressure is a better predictor of cardiovascular risk.17 Studies18,19 show that systolic blood pressure should be the primary target of hypertension management. High blood pressure increases the pulse pressure, which is a potential independent risk factor for cardiovascular disease. In our study, there was a reduction in systolic blood pressure in the intracameral group, suggesting that intracameral mydriatics are safe for patients with cardiovascular risks. Adequate pupil dilation for cataract surgery reduces the risk for intraoperative complications such as posterior capsule tear, iris trauma, bleeding, and zonular fiber dialysis with or without vitreous loss. Despite studies reporting intracameral mydriatic agents produced adequate pupil dilation for phacoemulsification,9,12–16 additional maneuvers were required to further dilate the pupils in both groups in our study. This agrees with findings in a study by Lundberg and Behndig9 in which mechanical pupil dilation was required in both groups. Conversely, in a study by Nikeghbali et al.16 patients in the intracameral group did not require additional methods to maintain pupil dilation compared with the topical group.
INTRACAMERAL VS TOPICAL MYDRIATICS FOR PUPIL DILATION
In our study, zonular dehiscence occurred intraoperatively in 1 patient in the intracameral group. One patient in the topical group developed progressive shallowing of the anterior chamber intraoperatively. The complication was likely the result of misdirection of fluid into the vitreous cavity, causing anterior displacement of the lens and iris diaphragm (posterior infusion syndrome). Both complications could have been the result of underlying preexisting weak zonular fibers rather than poor pupil dilation. A limitation of this study was that Castroviejo calipers were used to measure the pupils. The optical properties of the cornea can magnify and anteriorly displace the image. Therefore, the pupil size measurements using these calipers might not represent the actual pupil size. To dilate the eyes of 200 patients, a box of minims phenylephrine hydrochloride 10.0% and 40 bottles of lidocaine hydrochloride blood pressure 1.0% are needed. These medications cost approximately US $16.00 and US $11.00, respectively. Thus, the total price for an intracameral mydriatic mixture to dilate the eyes of 200 patients is approximately US $27.00. Meanwhile, a 5 mL bottle of tropicamide 1.0% and phenylephrine 2.5% can be used to dilate the eyes of 25 patients and costs approximately US $2.00 and US $2.40, respectively. Therefore, approximately 8 bottles of each tropicamide and phenylephrine eyedrops are needed to dilate the eyes of 200 patients, with a cost approximating US $35.20. These figures show that intracameral mydriatics are more cost effective than topical mydriatics. However, the price of the medications varies from country to country. In conclusion, our study found that intracameral mydriatic agents were comparable to topical agents in dilating pupils for cataract surgery, even in Asian eyes. However, pupil dilation was slower in the intracameral group than in the topical group in the early stages of surgery. Further study to determine the cost effectiveness of these agents in cataract surgery is required.
2. 3.
4.
5.
6. 7.
8. 9. 10. 11.
12.
13.
14. 15.
16.
17.
WHAT WAS KNOWN
18.
Intracameral mydriatics are effective in dilating pupils in lightly pigmented eyes.
WHAT THIS PAPER ADDS Intracameral mydriatic agents were as effective as topical mydriatics in dilating heavily pigmented pupils for cataract surgery in Malaysian patients. The effect of pupil dilation increased toward the end of surgery in the intracameral group but decreased in the topical group. Pupil dilation was slower in the intracameral group than in the topical group in the early stages of phacoemulsification. Intracameral mydriatic agents might be useful to augment pupil dilation as opposed to their use as a sole dilating method.
19.
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Tocicol 1998; 82:19–22. Available at: http://onlinelibrary.wiley.com/doi /10.1111/j.1600-0773.1998.tb01392.x/pdf. Accessed June 9, 2017 Levine L. Effective degree of mydriasis with phenylephrine and tropicamide. Am J Optom Physiol Opt 1976; 53:774–785 Nicholson F, Clark KL, Brecker SJD, Smith SA. A pharmacological method for measuring the penetration of topical mydriatics in man. [letter]. Br J Clin Pharmacol 1982; 14:468–469. Available at: http://onlinelibrary.wiley.com /doi/10.1111/j.1365-2125.1982.tb02014.x/epdf. Accessed June 7, 2017 Saettone MF. Progress and problems in ophthalmic drug delivery. Business Briefing: Pharmatech 2002; 167–171. Available at: http://aciont.com/pdf /SaettoneOcularDrugDeliveryArticle.pdf. Accessed June 7, 2017 Patel PB, Shastri DH, Shelat PK, Shukla AK. Ophthalmic drug delivery system: challenges and approaches. Systemic Rev Pharm 2010; 1:113–120. Available at: http://www.sysrevpharm.org/sites/default/files/1-2_0.pdf. Accessed June 7, 2017 Claudia G. Systemic toxicity with topical ophthalmic medications in children. Paediatr Perinat Drug Ther 2006; 7:23–29 Kalyanaraman M, Carpenter RL, McGlew MJ, Guertin SR. Cardiopulmonary compromise after use of topical or submucosal a-agonists: possible added complication by the use of b-blocker therapy. Otolaryngol Head Neck Surg 1997; 117:56–61. Available at: http://journals.sagepub.com /doi/pdf/10.1016/S0194-59989770207-9. Accessed June 7, 2017 Rengstorff RH, Doughty CB. Mydriatic and cycloplegic drugs: a review of ocular and systemic complications. Am J Optom Physiol Opt 1982; 59:162–177 Lundberg B, Behndig A. Intracameral mydriatics in phacoemulsification cataract surgery. J Cataract Refract Surg 2003; 29:2366–2371 Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 2005; 31:664–673 €m C. Cataract surgery and pupil size in patients with diaZaczek A, Zetterstro betes mellitus. Acta Ophthalmol Scand 1997; 75:429–432. Available at: http://www3.interscience.wiley.com/cgi-bin/fulltext/122407159/PDFSTART. Accessed June 7, 2017 C, Gallagher M, Thomson S. Safety of intraSoong T, Soultanidis M, Claoue cameral mydriasis in phacoemulsification cataract surgery. [letter]. J Cataract Refract Surg 2006; 32:375–376 Behndig A, Eriksson A. Evaluation of surgical performance with intracameral mydriatics in phacoemulsification surgery. Acta Ophthalmol Scand 2004; 82:144–147. Available at: http://www3.interscience.wiley.com/cgi-bin /fulltext/118808583/PDFSTART. Accessed June 7, 2017 Cionni RJ, Barros MG, Kaufman AH, Osher RH. Cataract surgery without preoperative eyedrops. J Cataract Refract Surg 2003; 29:2281–2283 Lee JJ, Moster MR, Henderer JD, Membreno JH. Pupil dilatation with intracameral 1% lidocaine during glaucoma filtering surgery. Am J Ophthalmol 2003; 136:201–203 Nikeghbali A, Falavarjani KG, Kheirkhah A. Pupil dilation with intracameral lidocaine during phacoemulsification: benefits for the patient and surgeon. Indian J Ophthalmol 2008; 56:63–64. Available at: http://www.ncbi.nlm.nih.gov /pmc/articles/PMC2636064/?reportZprintable. Accessed June 7, 2017 Strandberg TE, Pitkala K. What is the most important component of blood pressure: systolic, diastolic or pulse pressure? Curr Opin Nephrol Hypertens 2003; 12:293–297 Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham Heart Study. Circulation 1999; 100:354–360. Available at: http://circ.aha journals.org/content/100/4/354.long. Accessed June 7, 2017 ~es JB, Menezes PPO, Almeida de Sousa JM, Hermann JLV, Guimara Carvalho ACC. Evaluation of systolic, diastolic and pulse pressure as risk factors for severe coronary arteriosclerotic disease in women with unstable angina non-ST-elevation acute myocardial infarction. Arq Bras Cardiol 2004; 82:430–433. Available at: http://www.scielo.br/pdf/abc/v82n5 /en_20275.pdf. Accessed June 7, 2017
Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned.
First author: Amelia Lim Lay Suan, MD, M.Surg Ophthal
REFERENCES
Ophthalmology Department, Penang General Hospital, Georgetown Penang, Malaysia
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