Journal of Refractive Surgery

Original Article 

Effects of Short-term Preoperative Topical Ketorolac on Pupil Diameter in Eyes Undergoing Femtosecond Laser–Assisted Capsulotomy

Vasilios F. Diakonis, MD, PhD; Georgios A. Kontadakis, MD, MSc; Apostolos G. Anagnostopoulos, MD; Nilufer Yesilirmak, MD; Daniel P. Waren, MSPH; Florence Cabot, MD; Sonia H. Yoo, MD; Kendall E. Donaldson, MD, MS

Abstract

PURPOSE:

To assess pupil diameter before and after femtosecond laser–assisted capsulotomy in patients who were pretreated with a short-term topical nonsteroidal anti-inflammatory drug (NSAID) (ketorolac) versus those without pretreatment.

METHODS:

This prospective, randomized, observational case series included consecutive patients scheduled to undergo cataract extraction using the Catalys femtosecond laser platform (Abbott Medical Optics, Inc., Santa Ana, CA) to perform only capsulotomies. The same protocol for preoperative medical mydriasis was used for all patients, whereas pupil diameter was assessed using a surgical ruler immediately before and 3 minutes after femtosecond laser–assisted capsulotomy. The patients were divided into two groups: one received short-term topical ketorolac preoperatively and the other did not receive NSAID pretreatment (control).

RESULTS:

A total of 42 eyes of 42 patients (1 eye per patient) were included in the study. Mean pupillary miosis was 0.79 ± 1.08 and 1.57 ± 1.19 mm for the ketorolac and control groups, respectively. There was a statistically significant decrease in pupil diameter for both groups individually (P < .05). There was also a statistically significant difference between the two groups (P < .05) with the induced miosis in the eyes that did not receive topical NSAIDs prior to cataract extraction being twofold greater when compared with the miosis of the eyes that received ketorolac pretreatment.

CONCLUSIONS:

Short-term topical use of ketorolac prior to femtosecond laser–assisted cataract surgery seems to induce significantly less pupillary miosis in comparison to eyes that did not receive NSAID pretreatment. NSAID use is advised prior to femtosecond laser–assisted cataract surgery to minimize pupil miosis–related surgical difficulties or complications during cataract extraction.

[J Refract Surg. 2017;33(4):230–234.]

Abstract

PURPOSE:

To assess pupil diameter before and after femtosecond laser–assisted capsulotomy in patients who were pretreated with a short-term topical nonsteroidal anti-inflammatory drug (NSAID) (ketorolac) versus those without pretreatment.

METHODS:

This prospective, randomized, observational case series included consecutive patients scheduled to undergo cataract extraction using the Catalys femtosecond laser platform (Abbott Medical Optics, Inc., Santa Ana, CA) to perform only capsulotomies. The same protocol for preoperative medical mydriasis was used for all patients, whereas pupil diameter was assessed using a surgical ruler immediately before and 3 minutes after femtosecond laser–assisted capsulotomy. The patients were divided into two groups: one received short-term topical ketorolac preoperatively and the other did not receive NSAID pretreatment (control).

RESULTS:

A total of 42 eyes of 42 patients (1 eye per patient) were included in the study. Mean pupillary miosis was 0.79 ± 1.08 and 1.57 ± 1.19 mm for the ketorolac and control groups, respectively. There was a statistically significant decrease in pupil diameter for both groups individually (P < .05). There was also a statistically significant difference between the two groups (P < .05) with the induced miosis in the eyes that did not receive topical NSAIDs prior to cataract extraction being twofold greater when compared with the miosis of the eyes that received ketorolac pretreatment.

CONCLUSIONS:

Short-term topical use of ketorolac prior to femtosecond laser–assisted cataract surgery seems to induce significantly less pupillary miosis in comparison to eyes that did not receive NSAID pretreatment. NSAID use is advised prior to femtosecond laser–assisted cataract surgery to minimize pupil miosis–related surgical difficulties or complications during cataract extraction.

[J Refract Surg. 2017;33(4):230–234.]

Cataract surgery requires an adequate and stable mydriasis throughout the procedure to facilitate the creation of the anterior capsular opening (capsulorhexis or capsulotomy), the removal of the cataractous crystalline lens (nuclear phacoemulsification and cortical removal), and the insertion of the intraocular lens. All patients receive a combination of anesthetics and mydriatic agents immediately prior to cataract surgery to achieve surface anesthesia and pupillary mydriasis. However, intraoperative pupillary miosis often occurs due to release of inflammatory mediators such as prostaglandins (from the iris and ciliary body) into the anterior chamber.1 A small pupillary diameter during cataract extraction limits intraoperative visualization by reducing the surgical field and makes intraoperative maneuvers more challenging.2 This has been shown to increase the risks during cataract surgery, leading to serious sight-threatening complications such as posterior capsular tears, iris trauma, vitreous loss, retained lens material, cystoid macular edema, and retinal detachment.2,3

Pupillary miosis after femtosecond laser–assisted cataract surgery has been a subject of discussion since soon after the introduction of femtosecond laser technology.4–6 This phenomenon has been associated with the increase in prostaglandin concentrations in the anterior chamber immediately after femtosecond laser–assisted cataract surgery (femtosecond laser–assisted capsulotomy pretreatment) and has been attributed to gas release in the anterior chamber, lens protein release, increase in temperature, and vibrations/shockwaves due to laser emissions.7,8 All of the above are thought to trigger prostaglandin synthesis in the iris and ciliary body, a phenomenon that has also been associated with pupillary constriction following femtosecond laser–assisted capsulotomy.4–8 Recent reports have demonstrated that the use of short-term topical nonsteroidal anti-inflammatory drugs (NSAIDs) as a pretreatment prior to femtosecond laser–assisted capsulotomy results in significantly less prostaglandin synthesis in the anterior chamber, potentially preventing miosis induced by femtosecond laser–assisted capsulotomy.9

The following study assessed pupillary diameter before and after femtosecond laser–assisted capsulotomy in patients who were pretreated with short-term topical NSAIDs compared with those who did not receive pretreatment.

Patients and Methods

Patient Population

This prospective study included consecutive patients scheduled to undergo cataract extraction using femtosecond laser–assisted capsulotomy between June 2015 and June 2016. The femtosecond laser–assisted capsulotomy pretreatment included the creation of only the capsulotomy, using the Catalys laser platform (Abbott Medical Optics, Inc., Santa Ana, CA). The interface used in all cases was the Liquid Optics Interface 14-mm inner diameter (Abbott Medical Optics, Inc.). The same protocol for preoperative medical mydriasis was used for all patients, whereas pupil diameter was assessed immediately before and 3 minutes after femtosecond laser–assisted capsulotomy. The patients were divided into two groups: the ketorolac group (20 eyes) received short-term topical ketorolac preoperatively (four times per day for 3 days prior to cataract extraction) and the control group (22 eyes) did not receive NSAID pretreatment. Intraoperative assessment of the capsule outcomes was performed and was graded as one of the following four types: complete treatment pattern or free-floating (type 1), microadhesions (type 2), incomplete treatment pattern (type 3), and complete pattern but not continuous (type 4), as described by Nagy et al.10

All patients were informed of the risks and benefits prior to cataract surgery, and they gave written informed consent in accordance with institutional guidelines and the tenets of the Declaration of Helsinki for human research. Prior to the study, institutional review board approval 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 α-adrenergic-antagonist, history of poor pupillary dilation (less than 6 mm), or rheumatic disease were excluded from the study.

Cataract Surgery Technique

Medical mydriasis was performed using topical 1.0% tropicamide (Akorn Inc., Lake Forest, IL) eye drops and 2.5% phenylephrine (Paragon BioTeck Inc., Portland, OR) eye drops, instilled three times (every 10 minutes) within 1 hour prior to femtosecond laser–assisted capsulotomy (the last application of topical mydriatics was instilled 15 minutes prior to surgery). All procedures were performed under topical anesthesia and in the same operating room where both the femtosecond laser and phacoemulsification platforms were available (no need to change operating rooms or operating chairs). A 5-mm femtosecond laser capsulotomy was performed without corneal incisions or lens fragmentation. All patients received manual clear corneal incisions, followed by traditional phacoemulsification (Centurion; Alcon Laboratories, Inc., Fort Worth, TX). The capsulotomy settings were identical for all cases: the pattern was circular with a 5-mm diameter centered at the pupil and the incision depth was 600 µm. The horizontal and vertical spot spacing were 5 and 10 µm, respectively, whereas the pulse energy was 4 mJ. All eyes were injected intracamerally with non-preserved phenylephrine 1.5% and lidocaine 1% (compounded by the Bascom Palmer pharmacy) at the beginning of the traditional phacoemulsification procedure. All pupil measurements after femtosecond laser–assisted capsulotomy 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, whereas an intraocular lens was placed in the capsular bag in all cases.

Postoperatively, all patients received the same treatment: a combination of an antibiotic and steroid and NSAIDs.

Pupil Assessment

Immediately before and 3 minutes after femtosecond laser–assisted capsulotomy, the pupil diameter was measured three times using a surgical ruler by the surgeon (a single surgeon [KED] blind to the study performed the surgeries and the measurements). The average of the three measurements was used for statistical analysis. The measurements were performed using the same surgical ruler (millimeter increments) under the same surgical microscope (prior to anterior chamber penetration), using maximum luminance in all cases. The maximum horizontal pupil diameter was always assessed while the observer kept one eye closed during the measurement to avoid parallax-related errors.6

Statistical Analysis

Univariate comparisons between groups were performed using the two-sided Student's t test for continuous variables and the chi-square test or Fisher exact test for categorical variables. 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. Statistical analysis was performed using the SPSS statistical package (version 22; SPSS, Inc., Chicago, IL). A P value of .05 or less was considered statistically significant.

Results

There were 42 patients in the study (12 men and 30 women) aged 66.64 ± 9.36 years (range: 50 to 90 years). One eye was included per patient. There was no statistically significant difference between the two groups in terms of age (P > .05). Post hoc analysis revealed a power of 0.6 for the study. All capsulotomies in both groups were graded as type 1 (complete capsulotomies).

Mean pupillary diameter before femtosecond laser–assisted capsulotomy pretreatment was 7.68 ± 0.83 mm (range: 6.5 to 9.5 mm) for the ketorolac group and 8.02 ± 0.51 mm (range: 6.5 to 9.0 mm) for the control group; there was no statistically significant difference between the groups regarding preoperative pupil diameter (P > .05). Mean pupil diameter 3 minutes after femtosecond laser–assisted capsulotomy was 6.89 ± 0.96 mm (range: 5.0 to 8.0 mm) for the ketorolac group and 6.45 ± 1.41 mm (range: 3.5 to 9.0 mm) for the control group. Mean pupillary miosis was 0.79 ± 1.08 mm (range: 0 to 4.5 mm) for the ketorolac group and 1.57 ± 1.57 mm (range: 0 to 4.0 mm) for the control group. There was a statistically significant decrease (comparison of preoperative and postoperative) in pupil diameter (miosis) for both groups individually (P < .05). Finally, there was also a statistically significant difference between the groups (P = .03), with a twofold higher degree of induced miosis in the eyes that did not receive topical NSAID pretreatment compared with the miosis of the eyes that received NSAID pretreatment.

None of the eyes in either group undergoing femtosecond laser capsulotomy demonstrated a pupil diameter less than 6 mm (making femtosecond laser–assisted capsulotomy feasible in all cases and allowing at least a 1-m distance between the pupillary border and the attempted capsulotomy in all cases) (Table 1). After femtosecond laser–assisted capsulotomy, none of the eyes (0%) in the ketorolac group and 4 eyes (18.2%) in the control group demonstrated a miotic pupil, reaching a level of clinically significant risk for cataract extraction (pupil diameter less than 5 mm) (Table 1). Five eyes (25%) in the ketorolac group and 4 eyes (18.2%) in the control group demonstrated a small pupil diameter (between 5 and 6 mm) after femtosecond laser–assisted capsulotomy pretreatment. Fifteen eyes (75%) in the ketorolac group and 14 eyes (63.6%) in the control group demonstrated a pupil diameter of greater than 6 mm after femtosecond laser–assisted capsulotomy (Table 1).


Pupil Diameter Before and After Femtosecond Laser–Assisted Capsulotomy

Table 1:

Pupil Diameter Before and After Femtosecond Laser–Assisted Capsulotomy

Discussion

Several studies have demonstrated that femtosecond laser–assisted capsulotomy induces significant miosis.4–6 Bali et al.5 reported that 9.5% of the patients undergoing femtosecond laser–assisted capsulotomy demonstrated significant pupil constriction. A prior study from our institute assessed the effect of three different laser platforms after femtosecond laser–assisted capsulotomy pretreatment and also revealed similar outcomes, with significant pupillary miosis associated with all three laser platforms.6 It is postulated that pupillary miosis is associated with the dissipation of energy into the anterior chamber and possibly with prostaglandin release in close proximity to the undersurface of the iris causing a decrease in pupillary diameter.5,6 In support of the above theory, Schultz et al.7 assessed the levels of prostaglandins in the aqueous humor after femtosecond laser–assisted capsulotomy 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. Other studies associate pupillary miosis with the total time of laser application and the patient's age,8 whereas suction time (of the patient interface) has not been associated with pupillary miosis.8

Topical NSAIDs have been used to minimize pupillary miosis during cataract surgery since the mid-1980s. All intraocular manipulations cause breakdown of the blood–aqueous barrier, promoting an inflammatory cascade with the release of prostaglandins by the nonpigmented epithelial layer of the ciliary body.11–14 Topical NSAIDs block cyclooxygenase and thereby inhibit the synthesis of prostaglandins, reducing inflammation in the anterior chamber and minimizing pupillary miosis.15–17 A study by Schultz et al. revealed that the use of topical NSAIDs prior to femtosecond laser–assisted capsulotomy reduced prostaglandin release in the anterior chamber of patients undergoing cataract extraction.9 The authors suggested that the use of NSAIDs has the potential to limit intraoperative laser-induced miosis. In support of the above hypothesis, our study showed that the patients receiving a 3-day topical pretreatment with NSAIDs before femtosecond laser–assisted capsulotomy retained their mydriasis better after the laser treatment.

We evaluated pupillary diameter after femtosecond laser–assisted capsulotomy only, using a single laser platform and the same capsulotomy settings. Our approach was targeted to control the induced surgical trauma as much as possible (only femtosecond laser capsulotomy) and also to avoid cataract density disparities between the patients to influence our outcomes (increase the variables of the current study). Furthermore, the patients in both groups were matched for age and preoperative pupil diameter. Our study demonstrated significant pupil miosis in all eyes of our cohort, even after femtosecond laser–assisted capsulotomy. These findings were similar to the published study by Schultz et al., which demonstrated that capsulotomy creation seems to be the main triggering factor for prostaglandin release in the anterior chamber when compared to lens fragmentation.18 This could be attributed to the close proximity of the treatment application to the iris and ciliary body during capsulotomy, causing their response.

The findings of the current study suggest that even the shortest femtosecond laser–assisted capsulotomy treatment (capsulotomy) in terms of laser time exposure, laser energy used, and suction time in patients with no comorbidities that would influence pupil size may cause a significant decrease in pupil diameter. Furthermore, a 3-day pretreatment with topical NSAIDs prior to femtosecond laser–assisted capsulotomy seems to significantly inhibit miosis induced by femtosecond laser–assisted capsulotomy when compared with patients who did not receive pretreatment. Another important finding of our study was that 4 eyes (18.2%) in the control group demonstrated a pupil diameter of 5 mm or less after femtosecond laser–assisted capsulotomy (clinically significant miosis), whereas none of the eyes that received NSAIDs preoperatively revealed a pupil diameter of 5 mm or less. A pupil diameter below the 5-mm threshold significantly limits intraoperative visualization, making cataract extraction challenging, and potentially increases the risk for intraoperative pupil-related complications. The surgical field in cataract surgery is directly related to the pupillary surface, which follows a chi-square function (pupil radius – pupillary surface) and demonstrates an exponential decrease in surface area with the decrease of the radius. On average, a decrease of 1 mm of diameter (0.5-mm decrease of radius) between 10 and 7 mm decreases the surgical field by 21% (for every millimeter), whereas between 7 and 4 mm it decreases the surgical field 31%. Therefore, the smaller the pupil diameter, the greater the effect on the surgical field.

Although topical NSAIDs seem to inhibit pupillary constriction to some extent after femtosecond laser–assisted capsulotomy, significant miosis was also noted in those cases. In our institute, we have modified the protocol of pupil mydriasis in all patients undergoing femtosecond laser–assisted capsulotomy to avoid this phenomenon. Aside from the standard preoperative mydriatic regimen and NSAID 3-day pretreatment, we also inject preservative-free intracameral phenylephrine 1.5% and lidocaine 1% (compounded by the Bascom Palmer pharmacy). We find this approach to be efficient because adequate intraoperative mydriasis is achieved in almost all cases and we have not experienced any miosis-related complications following this protocol.

Our study is limited by the small number of eyes we included. Another important limitation of this study is the assessment of pupil size using a surgical ruler. Pupil measurement in a surgical setting limits the objective accurate options for measurement due to sterility concerns. For example, the use of an infrared pupilometer is not possible in a sterile environment. Although we understand the measurement limitations, the surgical ruler was used in a standardized way to minimize measurement and user-dependent 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 with 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.

Despite the above limitations, this study demonstrates that pupillary miosis after femtosecond laser–assisted capsulotomy in patients with no co-morbidities related to pupillary miosis is significant. Furthermore, the patients who did not receive topical NSAID pretreatment demonstrated a twofold decrease in their pupil diameter in comparison with patients who received the NSAID pretreatment. Surgeons need to be aware of and prepared for this phenomenon to avoid miosis-related complications during femtosecond laser–assisted capsulotomy. Pretreatment with topical NSAIDs is highly recommended to avoid potential miosis-related complications.

References

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Pupil Diameter Before and After Femtosecond Laser–Assisted Capsulotomy

GroupPreoperativePostoperative
NSAID pretreatment (20 eyes)
  < 5 mm0 (0%)0 (0%)
  ≤ 5 and ≤ 6 mm0 (0%)5 (25%)
  > 6 mm20 (100%)15 (75%)
No NSAID pretreatment (22 eyes)
  < 5 mm0 (0%)4 (18.2%)
  ≤ 5 and ≤ 6 mm0 (0%)4 (18.2%)
  > 6 mm22 (100%)14 (63.6%)
Total (42 eyes)
  < 5 mm0 (0%)4 (9.5%)
  ≤ 5 and ≤ 6 mm0 (0%)9 (21.4%)
  > 6 mm42 (100%)29 (69.1%)
Authors

From Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.

Drs. Yoo and Donaldson serve as speakers and consultants for Alcon and Abbott Medical Optics. Dr. Diakonis received a scholarship (2014) from the Hellenic Society of Intraocular Implants and Refractive Surgery for fellowship training. The remaining authors have no financial or proprietary interest in the materials presented herein.

AUTHOR CONTRIBUTIONS

Study concept and design (VFD, DPW); data collection (VFD, GAK, AGA, NY, DPW, FC, SHY, KED); analysis and interpretation of data (VFD, GAK, NY, DPW); writing the manuscript (VFD, GAK, AGA, NY, FC); critical revision of the manuscript (VFD, DPW, SHY, KED); statistical expertise (VFD); supervision (SHY, KED)

Correspondence: Vasilios F. Diakonis, MD, PhD, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 N.W. 17th Street, Miami, FL 33136. E-mail: diakonis@gmail.com

Received: October 07, 2016
Accepted: January 03, 2017

10.3928/1081597X-20170111-02

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