Femtosecond lasers were introduced in ophthalmology in 2001 and used strictly for corneal procedures, such as LASIK flap creation,1 tunnel formation for intracorneal ring segment insertion,2 pocket creation for intracorneal inlay insertion,3 arcuate keratotomies for corneal astigmatism correction,4 anterior lamellar keratoplasty,5 and penetrating keratoplasty.6 None of these corneal interventions required pupil mydriasis; thus, alterations in pupil diameter (eg, intraoperative miosis) were never a concern. Today, femtosecond lasers are being used for intraocular surgery and more specifically for cataract extraction.7 An adequate pupillary diameter is necessary for femtosecond laser-assisted cataract surgery (FLACS) to be used for capsulotomy creation and crystalline lens fragmentation. Furthermore, retention of mydriasis facilitates safe and efficient phacoemulsification after femtosecond laser pretreatment.
Several studies have demonstrated that FLACS induces significant miosis. Bali et al.8 reported that 9.5% of patients undergoing FLACS demonstrated pupil constriction that had to be addressed using topical mydriatics prior to phacoemulsification. The authors postulated that pupillary miosis was associated with the dissipation of energy into the anterior chamber and possibly with prostaglandin release in close proximity to the undersurface of the iris.8 In support of the above theory, Schultz et al.9 assessed the levels of prostaglandins in the aqueous humor after FLACS and reported a significant increase that was independent of the age of the patient, cataract density, suction time, laser time, and the potential creation of clear corneal incisions. Finally, Jun et al.10 associated pupillary miosis with the total time of laser (FLACS) application and the patient's age. Suction time was not associated with pupillary miosis in that study.10
This study assessed and compared the effect of FLACS on pupil diameter using three different laser platforms.
Patients and Methods
This prospective study included consecutive patients scheduled to undergo cataract extraction using FLACS between August 2013 and February 2015. All eyes received FLACS pretreatment using three laser platforms: LenSx (Alcon Laboratories, Inc., Fort Worth, TX; 79 eyes), Catalys (Abbott Medical Optics Inc., Santa Ana, CA; 68 eyes), and Victus (Bausch & Lomb, Inc., Rochester, NY; 51 eyes). The same protocol for preoperative medical mydriasis was used for all patients, and pupil diameter was assessed immediately before and 3 minutes after FLACS.
All patients were informed of risks and benefits prior to cataract surgery and gave written informed consent in accordance with institutional guidelines and the tenets of the Declaration of Helsinki for human research. Prior to the study, approval from the University of Miami institutional review board was obtained.
Inclusion and Exclusion Criteria
Patients were strictly screened and included in the study only if they had an unremarkable ocular history. Patients receiving topical treatment for glaucoma or any other disease, patients with inflammatory eye disease, previous ocular surgery or trauma, diabetes mellitus, pseudoexfoliation, history of treatment with an alpha-adrenergic antagonist, history of poor pupillary dilation (< 5 mm), or rheumatic disease were excluded from the study.
Settings of Femtosecond Laser Platform
For the Catalys group, capsulotomy energy was 4 µJ and lens fragmentation pattern was 4 quadrants with a grid of 500 micron spacing. Energy was 8 µJ for the anterior lens and 10 µJ for the posterior lens. The primary incision energy was 6 µJ and the secondary incision energy was 6.5 µJ. For the LenSx group, capsulotomy energy was 5 µJ, lens fragmentation pattern was 5 circular zones, and energy was 6 µJ. The primary incision energy was 5 µJ and the secondary incision energy was 6 µJ. For the Victus group, capsulotomy energy was 6.6 µJ, lens fragmentation pattern was 8 radial cuts, and energy was 8 µJ. The primary incision energy was 1.5 µJ and the secondary incision energy was 1.5 µJ.
Cataract Surgery Technique
Medical mydriasis was performed using topical 1.0% tropicamide eye drops (Akorn Inc., Lake Forest, IL) and 2.5% phenylephrine eye drops (Paragon BioTeck, Inc., Portland, OR), instilled three times (every 10 minutes) within 1 hour prior to FLACS (the last application of topical mydriatics was instilled 15 minutes prior to surgery). All procedures were performed under topical anesthesia. The femtosecond laser-assisted pretreatment included capsulotomy, crystalline lens fragmentation in all eyes, and in some cases two clear corneal incisions (1 primary and 1 secondary). Patients who did not receive femtosecond laser clear corneal incisions received manual clear corneal incisions using a keratome followed by traditional phacoemulsification (Centurion; Alcon Laboratories, Inc.). All eyes were injected intracamerally with anesthetics in combination with mydriatic agents (Bascom Palmer pharmacy, phenylephrine 1.5% and lidocaine 1% preservative free for intraocular use) at the beginning of the traditional phacoemulsification procedure. All pupil measurements after FLACS were made prior to opening corneal incisions and injecting intracameral agents. No intraoperative complications were noted in any of the cases included in the study. An intraocular lens was placed in the capsular bag in all cases.
Postoperatively, all patients received the same treatment: a combination of an antibiotic, steroid, and nonsteroidal anti-inflammatory agent.
Immediately before and 3 minutes after FLACS, the pupil diameter was measured three times using a surgical ruler by the surgeon (three surgeons performed the measurements: SHY, KED, and TPO). The average of the three measurements was used for statistical analysis. The measurements were performed using the same surgical ruler (millimeter increments) under the surgical microscope prior to anterior chamber penetration. Pupil diameter was always assessed under the surgical microscope using the lowest illumination possible, whereas the operating room was fully illuminated. Furthermore, the pupil position in all patients was placed parallel to the floor and perpendicular to the microscope light to avoid pupil tilt and poor pupil diameter measurement. The maximum horizontal pupil diameter was always assessed, and the observer kept one eye closed during the measurement to avoid parallax-related errors.
Excel 2007 (Microsoft; Microsoft Corporation, Redmond, WA) and a customized Ophthalmic Data Analysis Software by Dr. Georgios A. Kounis (©2014 GNEMS, Chalkida, Greece) were used for data collection and analysis. Pupil diameter values before and after FLACS were analyzed using one-way analysis of variance (ANOVA) and post hoc tests. An evaluation for power analysis was conducted using post hoc power assessment. To assess the repeatability of the pupil diameter measurements, measurement error and statistical analysis were performed using techniques described by Bland and Altman. A P value less than .05 was considered statistically significant.
A total of 198 eyes of 161 patients were included in the study (in total, the cohort included 358 eyes that underwent FLACS during the same time period). One hundred sixty eyes were excluded from the study because they did not meet the inclusion criteria. Sixty-eight male and 93 female patients with a mean age of 69.58 ± 10.18 years (range: 38 to 92 years) were included. Post hoc analysis revealed a power of 1.0 for the LenSx platform (79 eyes), 0.96 for the Catalys platform (68 eyes), and 0.13 for the Victus platform (51 eyes). The laser platforms for the LenSx and Catalys groups demonstrated significant power; on the contrary, the Victus group did not demonstrate significant power. Because pupillary miosis in the Victus group was small, the necessary number of eyes needed to achieve significant power would exceed 500.
No eyes undergoing FLACS pretreatment in this study demonstrated a pupil diameter of less than 5 mm, making FLACS feasible in all cases. Table 1 lists pupil size before and after FLACS. Overall, 8 eyes (4.0%) demonstrated a pupil diameter of 5 mm or less after FLACS (miotic pupil is clinically significant for cataract extraction) and 48 eyes (24.24%) demonstrated a pupil diameter of 6 mm or less (small pupil diameter for cataract extraction).
Pupil Diameter for the Three Groups Before and After FLACS
Mean pupil diameter before FLACS pretreatment was 7.96 ± 0.79 mm (range: 5.5 to 9.5 mm), 7.94 ± 0.78 mm (range: 6.5 to 10 mm), and 7.54 ± 0.78 mm (range: 6 to 9.5 mm) for the LenSx, Catalys, and Victus groups, respectively. One-way ANOVA of pupil diameter before FLACS among the three groups demonstrated a significant difference (P = .006); post hoc analysis revealed a significantly smaller pupil diameter in the Victus group when compared to the LenSx (P = .01) and Catalys (P = .017) groups, whereas there was no significant difference between the LenSx and Catalys groups (P = 1.00).
Mean pupil diameter 3 minutes after FLACS was 6.54 ± 1.34 mm (range: 3.5 to 9.5 mm), 7.29 ± 1.14 mm (range: 3.5 to 10 mm), and 7.40 ± 0.82 mm (range: 6 to 9 mm) for the LenSx, Catalys, and Victus groups, respectively. One-way ANOVA of pupil diameter after FLACS among the three groups demonstrated a significant difference (P = .001); post hoc analysis revealed a significantly smaller pupil diameter in the LenSx group when compared to the Catalys (P = .001) and Victus (P = .001) groups. There was no significant difference between the Catalys and Victus groups (P = 1.00).
Mean pupillary miosis was 1.42 ± 1.26 mm (range: 0 to 4.5 mm), 0.66 ± 0.89 mm (range: 0 to 5 mm), and 0.14 ± 0.34 mm (range: 0 to 1 mm) for the LenSx, Catalys, and Victus groups, respectively. One-way ANOVA of pupillary miosis among the three groups demonstrated a significant difference (P = .001); post hoc analysis revealed a significantly smaller pupil diameter among all three groups, with LenSx inducing the highest degree of miosis, followed by Catalys, and finally Victus (P < .05).
There was a statistically significant decrease (before and after FLACS) in pupil diameter (miosis) for all groups individually (P < .05). There was also a correlation of pupil diameter before FLACS and pupillary miosis. Larger pupil diameter prior to FLACS was prone to higher degrees of miosis (P = .002). Finally, the error of measurement of the pupil diameter (the standard deviation of measurement) was not related to the magnitude of measurement as indicated by both the regression analysis and the techniques described by Bland and Altman (P = .35).
Pupillary mydriasis is essential for safe and efficient cataract extraction.11 In our study, we assessed the diameter of the pupil before and after FLACS pretreatment and compared the outcomes among three laser platforms. Our results are in agreement with the previously published literature7,8 because significant pupillary miosis was demonstrated after FLACS by all laser platforms used in the current study. The comparison of the laser platforms revealed a statistically significant difference, with LenSx inducing the highest degree of miosis, followed by Catalys, and finally by Victus. Furthermore, 16 eyes (8.1%) demonstrated a pupil diameter of 5 mm or less after FLACS (clinically significant miosis) and 42 eyes (21.21%) demonstrated a pupil diameter of 6 mm or less (small pupil diameter).
Even though pupillary miosis was also demonstrated in the Victus group, its magnitude was smaller when compared to the other platforms. We hypothesize that this difference is attributable to the increased intraocular pressure, which may reach more than 40 mm Hg12 with the Victus laser due to the vacuum system and corneal applanation process (for the other two systems, intraocular pressure does not exceed 30 mm Hg13). Elevated intraocular pressure has been associated with ocular ischemia. The Victus laser platform may potentially induce transient anterior segment ischemia that decreases circulation within the iris sphincter, and therefore does not allow the muscles to contract, inducing miosis after FLACS.14 Other factors could also be responsible for the small miosis induced by the Victus laser platform that need to be identified and assessed in future studies.
In our institute, we have modified the protocol of pupil mydriasis in all patients undergoing FLACS. Aside from the standard preoperative mydriatic regimen, we also inject intracameral anesthetics in combination with mydriatic agents. We find this approach to be efficient because adequate intraoperative mydriasis was achieved in all cases and we have not experienced any miosis-related complications following this protocol. In addition, all patients undergoing cataract surgery (traditional or FLACS) in our institute are pretreated for 3 days with nonsteroidal anti-inflammatory agents, which may facilitate pupillary dilation at the time of surgery.
Our study was limited by the fact that the Victus group did not include a sufficient number of eyes to achieve strong statistical significance. Because the degree of miosis in that group was small, we would require more than 500 eyes to meet the power analysis criteria for significance. Furthermore, we did not study the possible effect of time lapse after FLACS on pupil diameter. We performed phacoemulsification immediately after FLACS; this may not always be the case when the laser is situated outside the operating suite or due to work flow differences. Increasing degrees of pupillary miosis have been observed as more time elapses between FLACS pretreatment and phacoemulsification.15 Another limitation is the fact that the settings of the FLACS platforms in terms of energy expenditure (for capsulotomy, lens fragmentation, and clear corneal incision formation) and treatment patterns for lens fragmentation are not the same. This is a universal problem when comparing FLACS platforms because the settings may not be controlled and cannot be made identical. Furthermore, we did not match patient demographics (eg, age and sex) and ocular characteristics (eg, spherical equivalent, axial length, corneal refractive power, and cataract grade) of patients included in the different groups of the current study. Therefore, although all groups demonstrated significant pupil miosis, the differences among the three platforms might have been the result of the unmatched patient demographics and ocular characteristics among the study groups.
The most important limitation of this study is the assessment of pupil size using a surgical ruler. Pupil measurement in a surgical setting significantly limits the objective and accurate options for measurement for sterility concerns. For example, the use of an infrared pupilometer is not possible in a sterile environment. Additionally, the crystalline lens reflectance following FLACS fragmentation does not allow for accurate pupil measurements with a pupillometer. Although we understand the measurement limitations, the surgical ruler was used in a standardized way to minimize measurement and user errors. For this reason, all pupil diameter measurements were performed under the surgical microscope with the surgical ruler in close proximity to the surface of the eye and the surgical microscope luminance facilitating visualization. Furthermore, the observer always kept one eye closed to avoid parallax-related errors. Finally, the measurements taken in this study seem to be repeatable as demonstrated by statistical analysis. Another limitation of this study is the fact that neither the patient (cataract grade) nor laser (treatment pattern) characteristics were homogenous among the three groups studied.
Despite the above limitations, this study demonstrates that pupillary miosis after FLACS is significant in all of the laser platforms used. Surgeons need to be aware of and prepared for this phenomenon to avoid miosis-related complications during FLACS. Pretreatment with topical nonsteroidal agents and intracameral mydriatics is highly recommended to prevent potential miosis-related complications. Through the use of these two measures, surgeons can achieve and maintain adequate dilation for safe and effective phacoemulsification following FLACS pretreatment.
- Ratkay-Traub I, Juhasz T, Horvath C, et al. Ultra-short pulse (femtosecond) laser surgery: initial use in LASIK flap creation. Ophthalmol Clin North Am. 2001;14:347–355.
- Kubaloglu A, Sari ES, Cinar Y, Koytak A, Kurnaz E, Ozertürk Y. Intrastromal corneal ring segment implantation for the treatment of keratoconus. Cornea. 2011;30:11–17. doi:10.1097/ICO.0b013e3181e2cf57 [CrossRef]
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- Abbey A, Ide T, Kymionis GD, Yoo SH. Femtosecond laser-assisted astigmatic keratotomy in naturally occurring high astigmatism. Br J Ophthalmol. 2009;93:1566–1569. doi:10.1136/bjo.2008.149971 [CrossRef]
- Yoo SH, Kymionis GD, Koreishi A, et al. Femtosecond laser-assisted sutureless anterior lamellar keratoplasty. Ophthalmology. 2008;115:1303–1307. doi:10.1016/j.ophtha.2007.10.037 [CrossRef]
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- Schultz T, Joachim SC, Kuehn M, Dick HB. Changes in prostaglandin levels in patients undergoing femtosecond laser-assisted cataract surgery. J Refract Surg. 2013;29:742–747. doi:10.3928/1081597X-20131021-03 [CrossRef]
- Jun JH, Hwang KY, Chang SD, Joo CK. Pupil-size alterations by photodisruption during femtosecond laser-assisted cataract surgery. J Cataract Refract Surg. 2015;41:278–285. doi:10.1016/j.jcrs.2014.10.027 [CrossRef]
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- Baig NB, Cheng GP, Lam JK, et al. Intraocular pressure profiles during femtosecond laser-assisted cataract surgery. J Cataract Refract Surg. 2014;40:1784–1789. doi:10.1016/j.jcrs.2014.04.026 [CrossRef]
- Schultz T, Conrad-Hengerer I, Hengerer FH, Dick HB. Intraocular pressure variation during femtosecond laser-assisted cataract surgery using a fluid-filled interface. J Cataract Refract Surg. 2013;39:22–27. doi:10.1016/j.jcrs.2012.10.038 [CrossRef]
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Pupil Diameter for the Three Groups Before and After FLACS
|Group||< 5 mm||≥ 5 or ≤ 6 mm||> 6 mm|
|LenSx (n = 79 eyes)|
| Before FLACS||0 (0%)||0 (0%)||79 (100%)|
| After FLACS||6 (7.6%)||27 (34.2%)||46 (58.2%)|
|Catalys (n = 68 eyes)|
| Before FLACS||0 (0%)||0 (0%)||68 (100%)|
| After FLACS||2 (2.9%)||8 (11.8%)||58 (85.3%)|
|Victus (n = 51 eyes)|
| Before FLACS||0 (0%)||2 (3.9%)||49 (96.1%)|
| After FLACS||0 (0%)||5 (9.8%)||46 (90.2%)|
|Total (n = 198 eyes)|
| Before FLACS||0 (0%)||2 (1%)||196 (99%)|
| After FLACS||8 (4.0%)||40 (20.2%)||150 (75.8%)|