Clinical Outcomes after Topography-based Corneal Laser Surgery with the. WaveLight Oculyzer and Topolyzer Platforms

Transcription

1 1 Clinical Outcomes after Topography-based Corneal Laser Surgery with the WaveLight Oculyzer and Topolyzer Platforms By Arthur B. Cummings, M.D. 1 and Nadia Mascharka, MSc 2 Corresponding Author: Arthur Cummings, M.D., Clinical Director, Wellington Eye Clinic, Dublin, Ireland Address: Wellington Eye Clinic, Suite 36, Beacon Hall, Beacon Court, Sandyford, Dublin 18, Ireland Telephone: Fax: abc@wellingtoneyeclinic.com Assistance with the preparation of this paper was provided by WaveLight AG. Dr. Cummings has no commercial or proprietary interest in WaveLight AG (Alcon Laboratories) or the products provided by these companies. Dr. Cummings does not serve as a consultant, reviewer, or evaluator for WaveLight AG. Nadia Mascharka is Product Manager Ophthalmology for WaveLight AG (Alcon Laboratories) and has a commercial and proprietary interest in this company. 1 Wellington Eye Clinic, Dublin, Ireland 2 WaveLight AG, Erlangen, Germany

2 2 Abstract Purpose: To explore the efficacy, safety, and predictability of topography-guided LASEK and LASIK treatments using the Allegro Oculyzer as compared to the Allegro Topolyzer platform (WaveLight AG). Methods: In this retrospective, non-comparative case series, 72 eyes were treated using Oculyzer data and 71 eyes were treated using Topolyzer data. 79 males and 64 females ranging in age from 21 to 63 years were included in the study. The 6 month post-operative UCVA and BSCVA of patients were compared to the pre-operative values. The data analysis was stratified based on the pre-operative refractions, separating patients into three categories: myopes, hyperopes, and mixed astigmats. Results: Of the pre-operative myopes in the Oculyzer group, 76% remained the same, 14% gained 1 line, and 5% gained 2 lines of visual acuity at 6 months. In the Topolyzer group, 69% remained the same, 25% gained 1 line, and 6% gained 2 lines of BSCVA. The outcomes of the pre-operative hyperopes and patients with mixed astigmatism are similarly reported. The difference in outcomes between the Oculyzer and Topolyzer cohorts in the myopes and patients with mixed astigmatism was not statistically significant. In the hyperopes, patients treated with the Oculyzer had superior UCVAs to those treated with the Topolyzer platform. Conclusions: This case series demonstrates that the Oculyzer and Topolyzer are both effective tools in topography-guided corneal laser surgery. In myopes and patients with mixed astigmatism, both systems were comparable in efficacy and safety. In the hyperopes, the resultant UCVA in the Oculyzer cohort was slightly superior.

3 3 Introduction Whether primary or secondary laser refractive surgery is contemplated, patients with symptoms such as glare, halos, and starbursts require a customized treatment. 1 The Allegretto Eye-Q system (WaveLight AG, Erlangen, Germany) provides five options for customization including: Wavefront Optimized ablation profiles Wavefront-guided ablation profiles Oculyzer (Pentacam)-guided - Scheimpflug using OcuLink software Topolyzer - Topography-guided (placido disk) using T-CAT (Topography-Guided Customized Ablation Treatment) software, or Custom-Q - Pre-determining the Q-value If the decision is made to proceed with a topography-guided treatment, surgeons can then select a treatment based on data generated by the Oculyzer or the Topolyzer. The Oculyzer and Topolyzer are diagnostic instruments that have been converted to Class 2b devices in order to use their data to modify an ablation profile. Oculink and T-CAT refer to the portal software on the laser s laptop that link the Oculyzer data via Oculink to the laser and the Topolyzer data via T-CAT to the laser. There are patients who have aberrations of too great a magnitude for accurate wavefront sensing. 2 The most common reason for an unacceptable wavefront map is that it can not be validated due to issues such as significant corneal irregularity, corneal or lens opacities, dry eye, keratoconus, or forme fruste keratoconus. 3-4 We found that, in the majority of cases where we were unable to obtain validated wavefront maps, that we were able to acquire good quality topography maps with both the Oculyzer and the Topolyzer. If a difference was found in the

4 4 quality of maps produced by these two devices, a treatment based on the best quality of validated data was used. The Oculyzer is optimally designed for use when the aberrations or irregularities are more centrally located and the Topolyzer, which captures 22,000 points of measurement with an interactive elevation map, 5 is optimally used when the irregularities are located more peripherally. The Topolyzer, a placido disk system, produces a central scotoma where the camera is located and central data must be extrapolated. On the other hand, the Oculyzer features a Scheimpflug rotating camera that scans the eye either 25 times or 50 times depending on the chosen setting. As a result, a wealth of data points is acquired for the central cornea. A wavefront-guided customized treatment assumes that most of a given patient's ocular aberrations can be corrected by reshaping the cornea. However, if a patient has normal topography but abnormal wavefront maps, a wavefront-guided treatment could actually induce aberrations in the cornea (Holland SP, Lin D. Topographically-directed PRK for irregular astigmatism following penetrating keratoplasty. Poster presented at: 2006 AAO Annual Meeting, Las Vegas, Nevada). The topography-guided ablation, which is a customized ablation that uses topography instead of a wavefront map as the basis for treatment, 6 is generally reserved for eyes in which aberrations exist at the level of the corneal surface. These eyes typically have a history of prior refractive surgery such as radial keratotomy or excimer ablations, which were decentered. The topography-guided ablation is also useful in eyes with severe corneal irregularities, which may include abrupt contour changes over a small area of the cornea caused by conditions such as dry eye syndrome, corneal scars and forme fruste keratoconus. Topography is the only measuring tool that can detect the hills and valleys produced by scarring

5 5 that block the visualization of aberrometry patterns from the retina. In addition, topographyguided procedures are also commonly used for the treatment of hyperopia, especially where angle kappa is present, as the topography-guided ablation profile automatically decenters the treatment to reduce the angle kappa. This retrospective, non-comparative case series compares the efficacy, safety, and predictability of topography-guided LASEK and LASIK treatments using the Allegro Oculyzer and the Allegro Topolyzer platforms. Materials and Methods Seventy-nine Caucasian males and 64 Caucasian females were included for analysis. The Oculyzer cohort had an age range of from 21 to 52 years, with a median age of 34 years. The Topolyzer cohort had an age range of from 26 to 63 years, with a median age of 36 years. Patients included in this analysis had pre-operative pachymetry greater than or equal to 460 microns (µm) for a LASEK procedure and greater than or equal to 500 microns for a LASIK procedure. In addition, LASEK patients were required to have an estimated post-procedure residual corneal bed of at least 380 microns. LASIK patients were required to have an estimated post-procedure residual corneal bed of at least 250 microns. Kanellopoulos, 1 in a study exploring topography-guided custom retreatments of symptomatic eyes, required that patients have enough corneal tissue to leave at least 280 µm of stromal bed after the planned retreatment, which is similar to the criteria adopted in this study. The corneal thickness and predicted stromal bed depth were based on pre-operative records and on pre-procedure pachymetry readings. Excluded ophthalmic conditions included clinically significant dry eyes, forme fruste keratoconus, and keratoconus. Patients who had collagen vascular disorders, uncontrolled diabetes, or who were pregnant were excluded from this analysis. 138 patients (96.5%)

6 6 underwent surgery as an initial refractive procedure, whereas 5 eyes (3.5%) underwent surgery as a secondary enhancement. The secondary enhancements included two cases of small optical zones, two cases of decentered optical zones, and one case of a small, decentered optical zone. All five cases had residual myopia and validated wavefront maps could not be acquired. The pre-operative evaluations of patients included refractions (manifest, cycloplegic, and wavefront), measurements of the uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), scotopic pupil size (Procyon P3000, Haag-Streit UK), and topography with both the Oculyzer and Topolyzer. The UCVA and BSCVA were evaluated under photopic conditions with a luminance level of 85 candela/m 2. Manifest refractions were performed using plus-to-blur and fogging techniques to confirm the spherical endpoint. In order to determine whether data generated by the Oculyzer or Topolyzer would drive the procedure, a number of factors were considered. For each study eye, four maps were taken using the Oculyzer and eight maps were taken using the Topolyzer as the number of maps captured by each system differs. In our experience, Oculyzer maps have been more repeatable than the Topolyzer maps, consistently measuring 100% of the cornea. Because of the greater variability we have observed with Topolyzer maps, we decided to capture eight maps and average the data. The portal software indicated that the average quality of data with the Topolyzer maps has ranged between measuring 90 to 100% of the cornea. The repeatability of the maps generated by both devices was compared and the more consistent method was used in planning the treatment. 1 When the maps were of comparable quality, if the topographical errors were more centrally located, within 3 millimeters (mm) of the central cornea, the Oculyzer platform was selected for

7 7 use in the treatment. If the corneal irregularities were situated more peripherally, outside the 3 mm central corneal zone, the Topolyzer platform was chosen for use in the treatment. The rationale for this determination was based on the design of the devices. With the Oculyzer, the beam of light rotates 360 degrees to capture the entire cornea with a higher density of points concentrated in the central cornea. In contrast, the Topolyzer is a placido disk system where a camera is used to image reflections from the corneal surface. Because the camera is positioned in the center of the topographer, there is a small area in the center of the topography map where data must be interpolated. Informed consent was obtained from the subjects after the nature of the procedure had been fully explained. The flaps in all primary cases required a diameter greater than 8.5 mm and were created using the Rondo microkeratome (WaveLight AG) or the Hansatome XP microkeratome (Bausch & Lomb). Any re-treatments were performed by re-lifting the flap. All LASEK and LASIK procedures were performed in the Wellington Eye Clinic, Dublin, Ireland by Dr. Cummings using the Allegretto Eye-Q 400 Hz excimer laser (WaveLight AG). All refractive procedures were completed from October 2006 to March The target refraction in all cases was a plano prescription with the exception of 4 eyes where was targeted in order to achieve monovision. UCVA, BSCVA, manifest refraction, and corneal topography were evaluated at 1 month, 3 months, and 6 months post-operatively. Statistical significance was accepted at the 95% confidence interval (P < 0.05).

8 8 Results The results are stratified into three parts based on the patient s pre-operative refractive status: myopia, hyperopia, or mixed astigmatism. Pre-operative Myopia Group In the Oculyzer cohort, there were 21 males and 13 females, with 5 receiving LASEK and 29 receiving LASIK. In the Topolyzer cohort, there were 13 males and 14 females, with 7 receiving LASEK and 20 receiving LASIK. Two of the Oculyzer cohort and two of the Topolyzer cohort were secondary enhancements. With regards to efficacy, the UCVA results at 6 months are shown in Figure 1. In the Oculyzer group (20 patients), the majority of patients (55%, 11 patients) achieved a UCVA of 20/15 and in the Topolyzer group (16 patients), the majority of patients (69%, 11 patients) achieved a UCVA of 20/15. In the two cohorts, the difference in the lines of visual acuity lost, remaining the same, or gained was not statistically significant by the t-test (P = 0.21). Comparing the BSCVA at 6 months, in the Oculyzer group (21 patients), 5% (1 patient) had a BSCVA of 20/25, 10% (2 patients) had a BSCVA of 20/20, 76% (16 patients) had a BSCVA of 20/15, and 10% (2 patients) had a BSCVA of 20/12.5. In the Topolyzer group (16 patients), 13% (2 patients) of patients had a BSCVA of 20/20 and 88% (14 patients) had a BSCVA of 20/15.

9 9 With regards to safety at 6 months, the results are shown in Figure 2. Comparing the preoperative BSCVA and the 6 month post-procedure BSCVA, in the Oculyzer group (15 patients), the majority of patients (73%, 11 patients) remained the same pre- and post-operatively. In the Topolyzer group (4 patients), 50% (2 patients) showed no change in BSCVA and 50% (2 patients) gained 1 line of visual acuity. Comparing the Oculyzer and Topolyzer groups, the difference in the number of visual acuity lines lost, remaining the same, or gained was not statistically significant by the t-test (P = 0.12). Pre-operative Hyperopia Group In the Oculyzer cohort, there were 11 males and 5 females, with all 16 patients receiving LASIK. In the Topolyzer cohort, there were 19 males and 14 females, with 1 receiving LASEK and 32 receiving LASIK. With regards to efficacy at 6 months, the results are shown in Figure 3. In the Oculyzer group (8 patients), 75% (6 patients) achieved a UCVA of 20/25. In the Topolyzer group (24 patients), 42% (10 patients) had a UCVA of 20/25 and 17% (4 patients) had a UCVA of 20/20. A comparison of lines of visual acuity lost, remaining the same, or gained in the Oculyzer and Topolyzer group revealed that the difference was not statistically significant by the t-test (P = 0.39). Examining the BSCVA post-procedure at 6 months, in the Oculyzer group (8 patients), 40% (4 patients) had a BSCVA of 20/25, 50% (5 patients) had a BSCVA of 20/20, and 10% (1 patient) had a BSCVA of 20/15. In the Topolyzer group (23 patients), 4% (1 patient) had a BSCVA of

10 10 20/50, 4% (1 patient) had a BSCVA of 20/30, 26% (6 patients) had a BSCVA of 20/25, 48% (11 patients) had a BSCVA of 20/20, and 17% (4 patients) had a BSCVA of 20/15. Addressing the safety of the procedure at 6 months, the results are shown in Figure 4. In the Oculyzer group (10 patients), 40% (4 patients) lost 1 line of BSCVA and 50% (5 patients) remained the same pre- and post-operatively. In the Topolyzer group (23 patients), 26% (6 patients) lost 1 line of BSCVA, 52% (12 patients) remained the same pre- and post-operatively, and 17% (4 patients) gained 1 line of BSCVA. The difference in the number of visual acuity lines lost, remaining the same, or gained in the Oculyzer and Topolyzer groups was not statistically significant by the t-test (P = 0.07). Pre-operative Mixed Astigmatism Group In the Oculyzer cohort, there were 12 males and 10 females with 4 patients receiving LASEK and 18 patients receiving LASIK. The Topolyzer cohort consisted of 3 males and 8 females, with 3 receiving LASEK and 8 receiving LASIK. One patient in the Oculyzer cohort had a secondary enhancement. In regards to the efficacy of the procedure at 6 months, the results are shown in Figure 5. In the Oculyzer group (9 patients), 22% (2 patients) had a UCVA of 20/30 and 33% (3 patients) had a UCVA of 20/20. In the Topolyzer group (4 patients), 50% (2 patients) had a UCVA of 20/100 and 50% (2 patients) had a UCVA of 20/20. The difference in the number of visual acuity lines lost, remaining the same, or gained in the Oculyzer and Topolyzer groups was not statistically significant by the t-test (P = 0.18).

11 11 Looking at the BSCVA at 6 months, in the Oculyzer group (15 patients), 7% (1 patient) had a BSCVA of 20/50, 7% (1 patient) had a BSCVA of 20/40, 7% (1 patient) had a BSCVA of 20/30, 20% (3 patients) had a BSCVA of 20/20, and 60% (9 patients) had a BSCVA of 20/15. In the Topolyzer group (4 patients), 25% (1 patient) had a BSCVA of 20/20 and 75% (3 patients) had a BSCVA of 20/15. Exploring the safety of the procedure at 6 months, the results are shown in Figure 6. In the Oculyzer group (15 patients), 20% (3 patients) lost 1 line of BSCVA and 73% (11 patients) remained the same pre- and post-operatively. In the Topolyzer group (4 patients), 50% (2 patients) remained the same pre- and post-operatively and 50% (2 patients) gained 1 line of BSCVA. The difference in the number of visual acuity lines lost, remaining the same, or gained in the Oculyzer and Topolyzer groups was not statistically significant by the t-test (P = 0.07). Tables 1 and 2 address the refractive predictability of the procedure at 6 months for all three cohorts and show that the predictability was good with both the Oculyzer and Topolyzer. This case series suggests that the predictability of achieving the target refraction with both devices in the pre-procedure myopic group was comparable. In the hyperopic group, the predictability was slightly better with the Oculyzer, but in the mixed astigmatism group, the predictability was slightly better with the Topolyzer. In some cases, it was found that the Oculyzer acquired good maps while the Topolyzer maps were not acceptable on the same eye. The Oculyzer maps were generally found to be consistently satisfactory.

12 12 Discussion Topography-guided procedures using two different topographical systems provided good outcomes in cases where wavefront maps could not be reliably acquired. Our experience with the WaveLight platform has shown that, in approximately 20 to 30% of seemingly normal eyes, good quality wavefront maps can not be acquired. It is our view that if wavefront maps cannot be validated, they should not be used for wavefront-guided treatments. The greatest potential for topography-guided treatments may be in severely aberrated corneas with decreased BSCVA for which even refraction is unreliable. The indications for topography-guided treatments include decentered ablations, the enlargement of the optical zone, irregular astigmatism following penetrating keratoplasty, 7-8 RK, asymmetrical astigmatism, keratoconus, and in hyperopic eyes with a decentered angle kappa. Because its measurements are based purely on the corneal surface, topography-guided treatments can also be used in cases with media opacities such as corneal scars. 6 It should also be noted that topography-guided treatments eliminate issues dealing with the pupil centroid as the pupil is undilated during topography and tomography as well as during the laser treatment. In comparison, wavefront maps must be acquired through dilated pupils while the surgery is performed with the pupil undilated, bringing the issue of a pupil centroid shift to the forefront. Topography-guided ablations attempt to re-contour the corneal surface to match an ideal curve and may have advantages over wavefront-guided treatments for complicated eyes. Holland and Lin (Holland SP, Lin D. Topographically-directed PRK for irregular astigmatism following penetrating keratoplasty. Poster presented at: 2006 AAO Annual Meeting, Las Vegas, Nevada) noted that in topography-guided treatments, the ablation profile is calculated based on the

13 13 topographical height maps, which are then adjusted based on the eye's overall refraction. With the Oculyzer, the ablation profiles are calculated from height maps obtained with the device. The Topolyzer creates customized algorithms by averaging up to eight topographical maps per eye and uses a Zernike-based algorithm to create an ablation profile that corrects for corneal irregularities. In addition, to preserve or re-establish the cornea s natural asphericity, it is possible to factor a Q-value into topography-guided treatments. 9 With primary treatments, the targeted Q-value was entered as the pre-operative value. For example, if the pre-operative value was -0.34, then was entered as the post-operative target. In secondary cases, the targeted Q-value was always entered as zero. In these cases, the pre-operative Q-values were always positive, indicating an oblate cornea. A disadvantage of topography-guided ablations is that, because the data concentrates mainly on the corneal contour, the procedure doesn t take into account the rest of the refracting media. Because topography-guided ablations only use data from the anterior corneal surface, one must compensate for the lack of refractive data collected by the topography system. This is accomplished by looking closely at the higher order ablation profile (the profile that the laser is going to use when the refraction is entered as zero or plano). A decision is made as to how much myopia or hyperopia the higher order ablation profile is going to induce and then, in order to compensate, the refraction entered into the ablation profile is modified. This is the basis of TNT (Topography Neutralization Technique) as described by Lin et al. 10 Other studies have explored the use of topography-guided ablations using the Allegretto Wave excimer laser in the treatment of aberrated corneas and decentered ablations and have found

14 topography-guided treatments to be of benefit Spadea and Di Gregorio 17 demonstrated the 14 safety and efficacy of this topography-guided approach in improving the BSCVA, contrast sensitivity, and aberrations of subjects. A further refinement was used in deciding whether the Oculyzer or the Topolyzer data would be used. Patients were asked to sketch the higher order errors that they were experiencing with their best spectacle-corrected vision and these higher order errors were compared to the higher order ablation profiles of the Oculyzer and Topolyzer platforms. In most cases, these higher order ablation profiles looked very similar if not identical, but when they differed, the ablation profile that best matched the patient s subjective complaints was selected. Specifically, patients were asked to describe or sketch a projected large white square and a smaller white dot looking through their full distance correction in the phoropter (see Figure 7). Patients were asked to sketch the edges of the square and we observed whether the edges were neat and tidy, blurred and smudged, whether there was a ghost image, or whether the corners were regular. When sketching the dot, we observed whether there was a halo around the dot, a half moon, or whether there were any spokes or starbursts radiating from the dot. These sketches served to illustrate the patient s higher order errors and provided us with additional information as to selecting the appropriate device for the treatment. We have found that, with experience in the use of these platforms, the ability to reliably achieve the predicted refractive outcome improves as does the ability to perfect the resultant visual quality. The Oculyzer, which uses tomography, is superior for use when the aberrations or irregularities are more centrally located in the cornea. This Scheimpflug technology is designed

15 15 to perform more central cornea data capture, but can be affected by eye movement and by any haze or clouding of the cornea such as sub-epithelial haze or arcus senilis. The Topolyzer, using the placido disk, is superior when the irregularities are located more peripherally. Placido disk technology is recognized as an accurate mode of obtaining topographical data, but does not provide full surface information and demonstrates less accuracy when the corneal issues are more centrally located. The limitation of this study is that it is a non-comparative case series rather than a randomized trial. However, because the optimal treatment selected was based on the repeatability of the maps and the location of the topographical errors, it would not have been possible to randomize patients as each case was treated with an individualized approach. This series shows that both the Oculyzer and Topolyzer provide good, comparable outcomes in pre-operative myopes and in patients with mixed astigmatism. The Oculyzer resulted in slightly better UCVAs in the pre-operative hyperopes. When a customized treatment is needed, but accurate wavefront maps cannot be acquired, topography-guided laser procedures are a sound treatment modality. References 1. Kanellopoulos JA. Topography-guided custom retreatments in 27 symptomatic eyes. J Refract Surg. 2005;21:S513-S Mrochen M, Krueger RR, Bueeler M, Seiler T. Aberration-sensing and wavefront-guided laser in situ keratomileusis: management of decentered ablation. J Refract Surg. 2002;18:

16 16 3. Chalita MR, Chavala S, Xu M, Krueger RR. Wavefront analysis in post-lasik eyes and its correlation with visual symptoms, refraction, and topography. Ophthalmology. 2004;111: Montague AA, Manche EE. CustomVue laser in situ keratomileusis treatment after previous keratorefractive surgery. J Cataract Refract Surg. 2006;32: Jankov M. Topography for corneal irregularities. Cataract & Refractive Surgery Today. 2004: Campbell C. Corneal topography in corneal ablations. In: McRae SM, Krueger RR, Applegate RA eds. Customized Corneal Ablation: The Quest for Supervision. Thorofare, NJ: SLACK Inc.; 2001: Mularoni A, Laffi GL, Bassein L, Tassinari G. Two-step LASIK with topography-guided ablation to correct astigmatism after penetrating keratoplasty. J Refract Surg. 2006;22: Rajan MS, O'Brart DP, Patel P, Falcon MG, Marshall J. Topography-guided customized laser-assisted subepithelial keratectomy for the treatment of postkeratoplasty astigmatism. J Cataract Refract Surg. 2006;32: Seiler T, Dastjerdi MH. Customized corneal ablation. Curr Opin Ophthalmol. 2002;13: Lin DT, Holland SR, Rocha KM, Krueger RR. Method for optimizing topography-guided ablation of highly aberrated eyes with the Allegretto Wave Excimer Laser. J Refract Surg. 2008;24:S Jankov MR, Panagopoulou SI, Tsiklis NS, Hajitanasis GC, Aslanides M, Pallikaris G. Topography-guided treatment of irregular astigmatism with the Wavelight excimer laser. J Refract Surg. 2006;22:

17 Kymionis GD, Panagopoulou SI, Aslanides IM, Plainis S, Astyrakakis N, Pallikaris IG. Topographically supported customized ablation for the management of decentered laser in situ keratomileusis. Am J Ophthalmol. 2004;137: Alessio G, Boscia F, La Tegola MG, Sborgia C. Topography-driven excimer laser for the retreatment of decentralized myopic photorefractive keratectomy. Ophthalmology. 2001;108: Lee DH, Seo SJ, Shin SC. Topography-guided excimer laser ablation of irregular cornea resulting from penetrating injury. J Cataract Refract Surg. 2002;28: Alessio G, Boscia F, La Tegola MG, Sborgia C. Corneal interactive programmed topographic ablation customized photorefractive keratectomy for correction of post-keratoplasty astigmatism. Ophthalmology. 2001;108: Knorz MC, Jendritza B. Topographically-guided laser in situ keratomileusis to treat corneal irregularities. Ophthalmology. 2000;107: Spadea L, Di Gregorio A. Enhancement outcomes after photorefractive keratectomy and laser in situ keratomileusis using topographically guided excimer laser photoablation. J Cataract Refract Surg. 2005;31:

18 18 Tables TABLE 1 Clinical Data for Eyes That Received Topography-Guided Laser Surgery with the ALLEGRO Oculyzer Myopia Group Hyperopia Group Mixed Astigmatism Group Pre-op 6-Month Post-op Pre-op 6-Month Post-op Pre-op 6-Month Post-op Number of eyes Number of. Eyes within 0 (0) 20 (95) 3 (19) 8 (80) 6 (27) 9 (60) ± 0.5 D (%) Sphere [Diopters] ± ± ± ± ± ± 0.67 (range) (-8.25 to -1.00) (-1.25 to 0.25) (0.25 to 4.75) (-1.25 to 0.25) (4.50 to -6.25) (-1.50 to 0.75) Confidence Interval (Sphere) 0.14* 0.28* 0.34* Cylinder [Diopters] ± ± ± ± ± ± 0.94 (range) (-2.5 to -0.25) (-0.75 to 0.0) (0.0 to 4.25) (-1.5 to 0.0) (-8.0 to 3.75) (-4 to 0.0) Confidence Interval (Cylinder) 0.11* 0.32* 0.47* * Level of significance α = 0.05 TABLE 2 Clinical Data for Eyes That Received Topography-Guided Laser Surgery with the ALLEGRO Topolyzer Myopia Group Hyperopia Group Mixed Astigmatism Group Pre-op 6-Month Post-op Pre-op 6-Month Post-op Pre-op 6-Month Post-op Number of eyes Number of Eyes within ± 0.5 D (%) 3 (11) 14 (88) 3 (9) 18 (78) 1 (9) 2 (50)

19 19 Sphere (Diopters) ± ± ± ± ± ± 1.01 (range) (-6.50 to -0.25) (-1.00 to -0.75) (0.00 to 4.75) (-2.0 to 0.75) (-1.5 to 5.75) (-1.50 to 0.25) Confidence Interval (Sphere) 0.19* 0.28* 0.99* Cylinder (Diopters) (range) ± 1.15 (-4.5 to -0.25) ± 0.26 (-0.75 to 0.00) 1.14 ± 1.18 (0.0 to 4.0) ± 0.51 (-1.25 to 0.75) ± 2.21 (-3.50 to 3.50) ± 0.0 Confidence Interval (Cylinder) 0.15* 0.32* - * Level of significance α = 0.05 Figure Legends Figure 1. Graph of the efficacy data for the pre-operative myopia group. This graph compares the uncorrected visual acuity results at 6 months for the Oculyzer (Oculink) and the Topolyzer (T-CAT) cohorts. The actual number of patients represented by the percentages is in parentheses. Oculink and T-CAT refer to the portal software on the laser s laptop that link the Oculyzer data via Oculink to the laser and the Topolyzer data via T-CAT to the laser. Figure 2. Graph of the safety data for the pre-operative myopia group. This graph compares the pre-operative BSCVA to the 6 month post-procedure BSCVA. The actual number of patients represented by the percentages is in parentheses. Figure 3. Graph of the efficacy data for the pre-operative hyperopia group. This graph compares the uncorrected visual acuity results at 6 months for the Oculyzer and the Topolyzer cohorts. The actual number of patients represented by the percentages is in parentheses. Figure 4. Graph of the safety data for the pre-operative hyperopia group. This graph compares the pre-operative BSCVA to the 6 month post-procedure BSCVA. The actual number of patients represented by the percentages is in parentheses.

20 20 Figure 5. Graph of the efficacy data for the pre-operative mixed astigmatism group. This graph compares the uncorrected visual acuity results at 6 months for the Oculyzer and the Topolyzer cohorts. The actual number of patients represented by the percentages is in parentheses. Figure 6. Graph of the safety data for the pre-operative mixed astigmatism group. This graph compares the pre-operative BSCVA to the 6 month post-procedure BSCVA. The actual number of patients represented by the percentages is in parentheses. Figure 7. This figure shows the visual quality when a patient looks at a projected white dot and a large white square with best correction. If there are no quality problems, then a wavefront optimized treatment is indicated (this does not include any higher order ablation profile). When there are visual quality issues present, then a topography-guided procedure is indicated if wavefront data of sufficient quality cannot be obtained. If both Topolyzer and Oculyzer data is available, then the higher order ablation profile (when the refractive data is entered as zero) that best matches the patient sketch of the aberrations is used.

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27 Figure 7: Images as seen by patient with full correction Ablation profile Higher Order Ablation Example 1: No complaints WFO profile No higher order ablation Example 2: Irregular halos, glare T-CAT ablation profile Higher order ablation Example 3: Irregular halos, glare Oculink ablation profile Higher order ablation