The Role of Iris Color in Femtosecond Laser-Induced Miosis in Patients Undergoing Annals of Clinical Cataract Surgery

open access Research Article

Ophthalmology Tarek Ibrahim, MD, PhD1,2, Phillip Goernert, PhD3 and Guillermo Rocha, MD, FRCSC, FACS1,4,5

1Ocular Microsurgery & Laser Centre, Brandon, Manitoba, Canada Received: Nov 28, 2017 2Eye Consultant Centre, Visiting Consultant, Dubai, UAE

3 Accepted: Dec 08, 2017 Department of Psychology, Brandon University, Manitoba, Canada 4Department of Ophthalmology, University of Manitoba, Canada Published: Dec 12 , 2017 5Brandon Regional Health Centre, Prairie Mountain Health, Manitoba, Canada

*CORRESPONDING AUTHOR: Abstract Tarek Ibrahim, University of Manitoba, GRMC, 144-6th Street, Brandon, Manitoba, Purpose R7A 3N2, Canada, Telephone: (647) 522- To measure Femtosecond laser (FSL)-induced miosis and to determine 0299; (204) 727-1954; if correlation with iris color exists in patients undergoing Femtosecond Email: [email protected] Laser Assisted Cataract Surgery (FLACS)

Methods KEYWORDSV Miosis; Femtosecond laser; Cataract Patients were divided into 3 groups based on iris color: blue (Group 1; N=62), hazel (Group 2; N=48) and brown (Group 3; N=27). Intra operative surgery; Iris color miosis was graded into 4 categories (from 0 to +3) following FSL use. FSL-induced miosis was observed preoperatively, immediately after FSL use, and immediately before phacoemulsification “shifting time”. FSL CITATION suction time and shifting time were also collected Tarek Ibrahim, Phillip Goernert and Guillermo Rocha. 2017. The Role of Iris Results

Color in Femtosecond Laser-Induced Of the 137 eyes, 82% of Group 1, 40% of Group 2, and 22% of Group 3 Miosis in Patients Undergoing Cataract showed miosis. Kruskal-Wallis test showed significance of eye color on Surgery. Ann Clin Opthamol. 2017 1(1) FSL-induced miosis (H (2) = 35.67, p < .01); Dunn Q tests of the groups’ mean rankings showed that the degree of FSL-induced miosis was 1001. significantly higher in the blue eye color group than in either other eye color group (both p-values < .05).The difference in the degree of FSL- induced miosis between the hazel and brown eye color groups was not significant (p > .05)

Conclusion

Light-colored irides may be more susceptible to FSL energy than darker irides. There is a significant relationship between blue color irides and pupillary constriction during post-FSL pre-treatment in cataract surgery. Clinical measures might be taken in light colored irides undergoing FLACS to avoid intra operative complications Copyright  Tarek Ibrahim Introduction Patients and Methods

When femtosecond laser (FSL) technology was introduced This study comprised eyes that underwent FLACS with in the early 2000s, it provided surgeons with new means to the Victus femtosecond laser platform (Bausch & Lomb, perform corneal procedures that ranged from corneal flap Bridgewater, NJ, USA) and phacoemulsification with the creation in laser in situ keratomileusis (LASIK) to penetrating Stellaris PC (Bausch&Lomb) at Brandon Regional Health Centre, keratoplasty, among others [1-6]. However, as pupil dilation is Manitoba, Canada, between October 2015 and March 2016. not necessary in LASIK so intraoperative miosis was neither The study was approval by the Research Ethics Board (REB) of debated nor analyzed. Manitoba University and was performed in accordance with the tenets of the Declaration of Helsinki. Advances in FSL technology have allowed surgeons to use these devices for portions of cataract surgery [7,8]. The Pupil dilation was recorded immediately before and immediately literature supports the use of FSL to improve the consistency after FSL and once the phacoemulsification began. To compare of capsulotomy in terms of size, shape, and centration, and the differences between light, medium, and dark irides, we to decrease ultrasound (U/S) power and time used during included patients with blue, brown, or hazel irides (Figures 1-3). phacoemulsification [7,9-11]. Two investigators (T.I. and G.R.) qualified iris color; if the two investigators disagreed or color was not apparent, those eyes Femtosecond laser-assisted cataract surgery (FLACS) were excluded from analysis. Other eye colors (e.g., green, gray, can be used for capsulotomy creation and crystalline lens violet) were not evaluated for study inclusion. fragmentation, but requires an adequate pupillary diameter to minimize complications. Nagy et al. [12], noted, for example, Miosis was graded into 0, +1, +2, and +3 depending on the degree that the FSL shockwaves created during use may affect the of pupillary constriction and anatomic factors, such as the surrounding tissue and recommended a 6.5 mm pupil for a 5 mm diameter capsulotomy, and a 6.0 mm pupil diameter for a 4.5 mm diameter capsulotomy. Adequate pupil dilation is an essential aspect of FSL pre-treatment to ensure safe and efficient phacoemulsification. Studies have shown that the prevalence of significant intraoperative miosis ranges between 10% and 32% [12-14]. To date, factors including patient age, FSL application time and energy dissipation, increased intraocular pressure during docking, the patient interface, and overall cataract density may be causal [12,14-17], but no single factor has been well correlated to FSL-induced miosis. In fact, the importance of an adequate pupil size is twofold: initially, to Figure 1: Blue Color Iris determine whether a suitably sized laser capsulotomy can be created (relevant to FLACS), and intraoperatively, to diminish the impact on complication rates during phacoemulsification,� irrigation/aspiration and intraocular lens implantation (relevant to both manual surgery and FLACS).

We postulated that light-colored irides may be more affected by the FSL beam than darker irides. To the best to our knowledge, this is the first evaluation of iris color as a factor for FSL-induced miosis.

Figure 2: Hazel Color Iris

Citation: Tarek Ibrahim, Phillip Goernert and Guillermo Rocha. 2017. The Role of Iris Color in Femtosecond Laser-Induced Miosis in Patients Undergoing Cataract Surgery. Ann Clin Opthamol. 2017 1(1) 1001.

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Iris color, pupil size (degree of miosis) before the procedure, pupil size (degree of miosis) immediately after FSL, and pupil size (degree of miosis) prior to phacoemulsification initiation were recorded. FSL suction time and shifting time (time between end of FSL and initiation of phacoemulsification) also were collected.

Subjects were enrolled in this study if they had an unremarkable ocular history, could achieve adequate pupillary dilation as determined by the surgeon (typically ≥ 6mm), and met the Figure 3: Brown Color Iris iris color mandates. Exclusion criteria included patients with history of intraocular surgery or trauma, pseudoexfoliation syndrome, glaucoma medication use, inflammatory eye disease, preoperative zonular weakness, systemic use of alpha- blockers for benign prostatic insufficiency (i.e., tamsulosin), or poor pupil dilation.

FSL settings are shown in Table 1. In all cases the primary incision was performed manually based on surgeon preference. All surgeries were performed in the same operating room where the FSL resides.

Figure 4: FSL Induced Miosis 0 Surgical technique

Patient preparation for surgery was done through a standing order for all cases. At arrival (one hour before surgery), patients were administered one tablet of lorazepam 0.5 mg sublingual (Pfizer Inc., New York, NY, USA); one drop of tetracaine hydrochloride 0.5% eye drops (Bausch + Lomb) was instilled bilaterally. The same protocol for preoperative medical mydriasis was used for all patients: A pre-prepared wick soaked with a mixture of tropicamide 1% (Alcon Laboratories, Ft. Worth, Texas, USA), phenylephrine 2.5% (Alcon Laboratories), Figure 5: FSL Induced Miosis +1 homatropine 2% (Alcon Laboratories), ketorolac 0.45% (Allergan, Dublin, Ireland) and moxifloxacin HCl ophthalmic solution 0.5% distance between capsulotomy and papillary margins (Figures 4-7). We used the following scales to grade the miosis: 0 miosis = no change in pupil size, +1 miosis = slight constriction from the pre-surgery pupil dilation (1 mm), +2 miosis = when the pupil is midway (2 mm constriction) between the starting position and the capsulotomy site; and +3 miosis = iris margin covers the capsulotomy (marked constriction). Pupil assessment was performed under the surgical microscope using the lowest illumination possible, with ambient illumination of the operating room. Patients were kept in a horizontal position with the observer keeping one eye closed during the measurement in order to avoid parallax-related errors. Figure 6: FSL Induced Miosis +2

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radial and three circular cuts were used in all cases), and two clear cornea 0.9mm side-ports in all eyes. The main incision (1.8 mm) was done manually using a keratome in all cases followed by phacoemulsification. All eyes were injected intracamerally with preservative-free anesthetics (lidocaine HCL 1%, Alveda Pharmaceuticals, Toronto, Canada) at the beginning of the phacoemulsification procedure. Single use povidone iodine 5% (Bausch + Lomb) was instilled in all cases at the start and at the end of the procedure. No intra operative complications were Figure 7: FSL Induced Miosis +3 noted. All patients received the same postoperative medical (Alcon Laboratories) was inserted into the inferior conjunctival treatment regimen: a combination of an antibiotic, steroid, and fornix of the operative eye for 15 minutes. The eye was checked; non steroidal anti-inflammatory agent. if adequate mydriasis was not achieved, another wick was inserted for another 15 minutes. All procedures were performed Statistical analysis under topical anesthesia. A Kruskal-Wallis test was used to show the effect of eye color FSL pre-treatment included capsulotomy (0.5 mm safety on FSL-induced miosis. Follow-up Dunn Q tests of the groups’ distance to pupil margin), crystalline lens fragmentation (four mean rankings was used to show the significance of the degree of miosis in relation to each eye color group. A p-value lower Table 1: Femtosecond laser parameters than 0.05 was considered statistically significant. Procedure Value Results Capsulotomy Diameter (mm) 5.2 A total of 137 eyes were enrolled in the study out of 422 eyes. Line spacing (μm) 4 Eyes excluded had different eye color than the established criteria, previous ocular morbidity or lack of adequate Spot spacing (μm) 5 mydriasis. All cases included in the study met the pre-operative Energy (μJ) 7.0/8.0 dilation requirements of at least 6mm pupillary diameter. Select Lens Fragmentation demographic data are provided in Table 2. Line spacing (μm) 10 Group 1 showed an overall rate of miosis of 82.26% (51/62/ Spot spacing (μm) 10 eyes); 51 eyes at the end of FSL application and four additional Energy (μJ) 08-Oct eyes after shift (6.45% after shift). Group 2 showed a rate of Radial cuts miosis of 39.58% (19/48 eyes) 19 eyes at the end of FSL Number 4 application and added no eyes after shift. Group 3 showed a rate of miosis of 22.22% (6/27 eyes); six eyes at the end of FSL Outer diameter (mm) 6.5 and one additional eye (3.71%) after shift. A Kruskal-Wallis test Circular cuts shows that there was a significant effect of eye color on FSL- Number 3 induced miosis (H (2) = 35.67, p < .01). Follow-up Dunn Q tests Outer diameter (mm) 2 of the groups’ mean rankings shows that the degree of FSL- Corneal (side-port) incisions induced miosis was significantly higher in Group 1 than in either Group 2 or Group 3 (both p-values < .05). The difference in the Line spacing (μm) 2.8 degree of FSL-induced miosis between Group 2 and Group 3 Spot spacing (μm) 5 was not significant (p > .05). There was no significant difference Energy (μJ) 2 in age, suction time, or shifting time across the three iris color groups (all p-values > .05), (Tables 3& 4).

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Discussion investigated previously. When intra ocular tissues undergo trauma (e.g cataract surgery), Numerous inflammatory factors Pupillary mydriasis is considered essential for safe and efficient may be released from the lens, iris, and trabecular meshwork cataract surgery [11]. Intraoperative miosis limits the surgeon’s [11,31]. Inflammatory cytokines interleukin (IL)-1β, IL-6, and ability to visualize the cataract and makes capsulorrhexis PGE2 have been found to increase significantly after FLACS in creation more challenging. Difficulties with small pupils the aqueous humor [11,31], which may be the cause of intra intra operatively can result in surgical complications such as operative miosis seen in these patients. In cases of +2 and posterior capsular tears, iris trauma, vitreous loss, retained lens +3 miosis, mostly blue irides, surgical measures such as intra material, cystoid macular edema, and retinal detachment [9,18]. cameral injection of mydriatics and/or the use of iris devices to properly dilate the pupil at the time of phacoemulsification may There are several situations and conditions that may contribute have to be undertaken. If the inflammatory factors are, indeed, to the inability to achieve or maintain adequate pupillary dilation the cause of intra operative miosis, our results show people during phacoemulsification, including pseudoexfoliation with blue irides are more susceptible to the femtosecond laser syndrome, posterior synechiae, elderly patients with atrophic beam than people with brown or hazel irides. These factors iris changes, and patients on chronic glaucoma medications would, therefore, activate more inflammatory cytokines and [18]. Despite the fact that these conditions are documented prostaglandins in people with blue irides. To the best of the at the time of patient preparation for surgery, at least 2% of authors’ knowledge, this marks the first report that suggests all cataract cases demonstrate surgically significant miosis blue eyes may be more susceptible to FSL energy. (pupil diameter of < 5 mm) [18]. Although phacoemulsification and FSL systems have improved capsulorrhexis and corneal In our study, we did not found statistical significant differences in wound reproducibility, there remains continued debate on the patient age (72.10 ±11.09), suction time (2.79 ± 0.59 minutes) or advantages of these FSL systems in terms of procedural safety shifting time (6.96 ± 0.83 minutes) and the FSL-induced miosis. and outcomes [19-23]. These findings disagree with findings in some studies that correlates exposure time of the tissue to the laser emissions A high incidence of intra operative miosis has been the and the increased prostaglandin release from intraocular tissues most frequently reported complication by FLACS surgeons [7,8]. Our shifting time is shorter than reported in those studies, [7,8,16,24,25]. One theory on the phenomenon is that laser however, as our FSL machine resides in the same OR. It is worth emissions applied to intraocular tissues might release cytokines mentioning that some studies had the same as ours although [26,27]. As a result of the cytokine release, prostaglandin the shifting time was up to 40minutes [30,32]. is released from the ciliary body into the anterior chamber [16,17,24,26]. Although the use of FSL - specifically the The maximum mydriatic effect should be taken into capsulotomy part of the procedure- may trigger prostaglandin consideration. One study reported that the maximum release, some authors believe the release is caused by mydriatic effect of several combinations of tropicamide and mechanical forces (suction or applanation) [18,28], while others phenylephrine lasted between 60 minutes and 75 minutes [32], suggest laser application time or shifting time between FSL pre- long enough to cover the 40 minutes needed to shift between treatment and the start of phacoemulsification may contribute laser pre-treatment and phacoemulsification. This may explain to the development of miosis [7,8]. why the shifting time and changes in the pupil area were not correlated in other studies. Our study assessed the diameter of the pupil before and after FSL and at the start of phacoemulsification to account for the We recommend special preparatory measures to be in place in shifting time. We found a significant decrease in the pupil area case a blue iris eye is undergoing FLACS. Proper preoperative after FSL pre-treatment, adding to the published literature on mydriasis, the preparation of intra cameral pupillary dilators the topic of FLACS-related complications [7,18,28-30]. and having access to iris devices are some of the measures that might be necessary in these cases. However, our study also found a significant correlation between FSL-induced miosis and iris color, which has not been Diakonis et al., compared FSL-induced miosis with different

Page 5/7 Copyright  Tarek Ibrahim machines, with the Victus machine incurring the least FSL- or method mentioned. induced miosis [27].The Victus uses high pressure during corneal applanation with its intelligent pressure sensors; these References may potentially induce transient anterior segment ischemia that decreases circulation within the iris sphincter, which in turn 1. Salomao MQ, Wilson SE. Femtosecond laser in laser in situ does not allow the muscles to contract to induce post-FLACS keratomileusis. J Cataract Refract Surgery. 2010; 36: 1024-1032. miosis [16, 33,34] 2. Yoo SH, Kymionis GD, Koreishi A, Goldman D, et al. We are aware of some limitations of this study, including the Femtosecond laser-assisted sutureless anterior lamellar keratoplasty. Ophthalmol. 2008; 115: 1303-1307. lack of an objective assessment of pupil size. Accurate and objective pupil measurement in a surgical setting is limited due 3. Steinert RF, Ignacio TS, Sarayba MA.”Top hat-shaped to sterility concerns. In our study, we based our measurement penetrating keratoplasty using the femtosecond laser. Am J on anatomic factors the distance between capsulotomy Ophthalmology 2007; 143: 689-691. and pupillary margins. We compensated for this disparity by 4. Abbey A, Ide T, Kymionis GD, Yoo SH. Femtosecond laser- assessing the pupil under the surgical microscope with the assisted astigmatic keratotomy in naturally occurring high lowest possible illumination. We also limited our observations astigmatism. Br J Ophthalmology. 2009; 93: 1566-1569. to only blue-, hazel-, or brown-colored eyes, as determined by two of the investigators. We cannot be certain our results would 5. Kubaloglu A, Sari ES, Cinar Y. Intrastromal corneal ring segment be duplicated in people with other-colored eyes, or that other implantation for the treatment of keratoconus. Cornea 2011; researchers would categorize patients’ eye color in a similar 30(1):11-17. manner. We attempted to overcome this potential limitation by 6. Bouzoukis DI, Kymionis GD, Limnopoulou AN. Femtosecond having two of the investigators categorize eye color separately. laser-assisted corneal pocket creation using a mask for inlay In cases where the investigators disagreed on eye color, the implantation. J Refract Surgery 2011; 27(11):818-820. patient was not included in the analysis. 7. Bali SJ, Hodge C, Lawless M. Early experience with the In conclusion, this study found a significant correlation between femtosecond laser for cataract surgery. Ophthalmology 2012; 119(5):891-899. blue irides and papillary constriction post FSL pre-treatment during cataract surgery. These results are clinically significant 8. Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical evaluation in that measures could be taken preoperatively in individuals of an intraocular femtosecond laser in cataract surgery. J Refract with blue irides, or considerations may be needed if the Surgery 2009; 25(12):1053-1060. FSL is not located in the same operating room as where the 9. Conrad-Hengerer I, Hengerer FH, Schultz T, Dick HB. phacoemulsification will take place. Effect of femtosecond laser fragmentation on effective phacoemulsification time in cataract surgery. J Refract Surgery Acknowledgments 2012; 28(12):879-883.

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