IDESIGN ADVANCED WAVESCAN STUDIO, STAR EXCIMER LASER SYSTEM

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) # I. GENERAL INFORMATION Device Generic Name: Ophthalmic Excimer Laser System Device Trade Name(s): iDesign Advanced WaveScan Studio System STAR S4 IR Excimer Laser System Device Procode: LZS Applicant's Name and Address: AMO Manufacturing USA, LLC. 510 Cottonwood Drive Milpitas, CA 95035 Date of Panel Recommendation: None Premarket Approval (PMA) Application Number: P930016/S045 Date of FDA Notice of Approval: November 14, 2016 The STAR Excimer Laser System™ was originally approved on March 27, 1996, under PMA P930016 (http://www.accessdata.fda.gov/cdrh_docs/pdf/p930016.pdf), for the limited indication for myopic photorefractive keratectomy (PRK) using a 6.0 mm ablation zone in patients 18 years of age or older with 1.0 to 6.0 diopters (D) of myopia with astigmatism of < 1.0 D whose refractive change for one year prior to treatment is within < 0.5 D. The original PRK indication was expanded in Supplement 3 (approved April 24, 1997), Supplement 5 (approved January 29, 1998), Supplement 7 (approved November 2, 1998), and Supplement 10 (approved October 18, 2000). The SSED to support each approval for PRK is available on the CDRH website. On November 19, 1999 (P990010), laser in-situ keratomileusis (LASIK) treatments was added to the approved indications, originally approved for use in patients 18 years of age or older for the reduction or elimination of myopia (nearsightedness) from 0 to -14.0 D with or without -0.50 to -5.0 D of astigmatism. The indication has been further expanded in Supplement 12 (approved April 27, 2001), Supplement 14 (approved November 16, 2001), Supplement 16 (approved May 23, 2003), Supplement 17 (approved December 14, 2004), Supplement 20 (approved March 17, 2005), Supplement 21 (approved August 3, 2005), and Supplement 44 (approved May 6, 2015). The SSED to support each approval for LASIK is available on the CDRH website. The applicant submitted Supplement 45 to further expand the wavefront-guided LASIK indications to include treatment of patients with mixed astigmatism. The updated clinical data to support the expanded indication is provided in this summary. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 1 {1} ## II. INDICATIONS FOR USE The STAR S4 IR Excimer Laser System and iDesign Advanced WaveScan Studio System is indicated for wavefront-guided laser assisted in situ keratomileusis (LASIK) in patients: - with mixed astigmatism as measured by iDesign Advanced WaveScan Studio™ System where the magnitude of cylinder (1.0 to 5.0 D) is greater than the magnitude of sphere, and the cylinder and sphere have opposite signs - with agreement between manifest refraction (adjusted for optical infinity) and iDesign Advanced WaveScan Studio System refraction as follows: - Spherical Equivalent: Magnitude of the difference is less than 0.625 D. - Cylinder: Magnitude of the difference is less than or equal to 0.5 D. - 18 years of age or older, and - with refractive stability (a change of ≤1.0 D in sphere or cylinder for a minimum of 12 months prior to surgery). ### III. CONTRAINDICATIONS The device is contraindicated: - in patients with collagen vascular, autoimmune or immunodeficiency diseases. - in pregnant or nursing women - in patients with signs corneal abnormalities including signs of keratoconus, abnormal corneal topography, epithelial basement membrane disease (EBMD) or degenerations of the structure of the cornea. - in patients with symptoms of significant dry eye. If the patients have severely dry eyes, LASIK may increase the dryness. This may or may not go away. Severe eye dryness may delay healing of the flap or interfere with the surface of the eye after surgery. It may result in poor vision after LASIK. - in patients whose corneal thickness would cause the anticipated treatment would violate the posterior 250 microns (μm) of corneal stroma. - in patients with advanced glaucoma. - in patients with uncontrolled diabetes. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 2 {2} # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the STAR S4 IR Excimer Laser System and iDesign Advanced WaveScan Studio System labeling. # V. DEVICE DESCRIPTION A. iDesign Advanced WaveScan Studio System The iDesign Advanced WaveScan Studio System incorporates wavefront aberrometry, auto-refractometry, corneal topography, keratometry, and pupillometry. The System measures the refractive error and wavefront aberrations of the human eye using a high-definition Hartmann-Shack wavefront sensor. The measurements can be used to determine regular (sphero-cylindrical) refractive errors and irregularities (aberrations) that may cause decreased or blurry vision in the human eye. The function of the Hartmann-Shack sensor is to measure the refractive error of the eye by evaluating the deflection of rays emanating from a small beam of light projected onto the retina and reflected back to the sensor off of the retina. To control the natural accommodation of the eye during iDesign Advanced WaveScan Studio system imaging, the system incorporates a fogged fixation target. The iDesign Advanced WaveScan Studio System optical head projects a beam of light onto the retina. The light reflects back through the optical path of the eye and into the wavefront device. The reflected beam is imaged by a lenslet array onto the charge-coupled device (CCD). Each lens of the array gathers light information (deflection information) from a different region of the pupil to form an image of the light that passes through that region of the pupil. An array of spots is imaged on the CCD sensor. The system compares the locations of the array of spots gathered from the CCD to the theoretical ideal (the ideal plane wave). The iDesign Advanced WaveScan Studio System software uses these data to compute the eye's refractive errors and wavefront aberrations using Fourier Transform analysis. The system displays the refractive errors and wavefront aberrations as the optical path difference (OPD) between the measured outgoing wavefront and the ideal plane wave. The iDesign Advanced WaveScan Studio system software subtracts the refractive errors from the wavefront errors map and displays the higher order aberrations as OPD errors. Regions of the pupil with positive OPD are in front of the ideal plane wave and areas with negative OPD are behind the ideal plane wave. The target treatment shape is automatically calculated by the iDesign Advanced WaveScan Studio system from the wavefront data. Once the target shape is established, the software generates the commands for the laser to create the target shape on the cornea. Corneal geometry, represented by the keratometry values, is PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 3 {3} taken into account in computing the laser instructions. Advanced CustomVue ablations for mixed astigmatism are approved for an optical zone of 6.0 mm, and an ablation zone of 9.0 mm. No treatments with a minimum optical zone greater than 6.0 mm were attempted in the U.S. Clinical Trial. The maximum iDesign Advanced WaveScan Studio system pupil size for treatment is 9.5 mm. All treatments utilized a variable repetition rate to a maximum of 20 Hz. Advanced CustomVue ablations for this PMA are locked out by the AMO Treatment Card below 1.0 D cylinder and above 6.0 D cylinder as measured by iDesign Advanced WaveScan Studio system. The final commercial release versions for Advanced CustomVue are iDesign Advanced WaveScan Studio system software version 1.3 and STAR S4 IR software version 5.32. The iDesign Advanced WaveScan Studio System software is capable of calculating mixed astigmatism treatments with an optical zone up to 6.5 mm with total ablation zone up to 9.5 mm. # B. STAR S4 IR Excimer Laser System The STAR S4 IR laser system is a 193 nm excimer laser system that delivers spatially scanning ultraviolet pulses of variable shape and size on to the cornea. Pulse shapes may be circles of variable diameter or slits of variable width and orientation. The range of diameters and slit widths available during treatments is 0.65 mm to 6.5 mm. An auto-centering dual camera infrared eye tracking system (ActiveTrak), together with the delivery system, aligns the treatment to the eye, and compensates for eye movements during laser correction to maximize the corneal reshaping accuracy. An operating microscope is used to observe the patient procedures and to facilitate accurate focus and laser beam alignment. A debris-removal system is designed to evacuate the debris plume that occurs during ablation. The operating chair and fixation LED align the patient, while a video camera and monitor records the patient treatment. The variable spot scanning (VSS) feature of the laser, used for Advanced CustomVue treatments delivers variable diameter ultraviolet pulses to precise locations by the scanning delivery system. The VSS algorithm optimizes the ablation pattern by choosing the best combination of beam diameters and locations to achieve a target shape. Wavefront-guided treatments using the STAR S4 IR and iDesign Advanced WaveScan Studio and WaveScan WaveFront Systems utilize an automated iris registration system. The angle of rotation of the patient's eye under the laser is determined by comparing features of the iris on the aberrometer image to the same features located in the image of the iris taken using the STAR S4 IR camera. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 4 {4} Features and components of the *STAR S4 IR* System include: - Excimer Laser - Gas Management System - Laser Beam Delivery System - Patient Management System - Computer Control - *AMO* Treatment Card C. Microkeratome The *Advanced CustomVue* procedure required the use of a commercially available keratome that has been cleared for marketing via premarket notification. The keratomes used in this study consisted of femtosecond ophthalmic surgical lasers that create a LASIK flap through precise individual microphotodisruptions of tissue, created by tightly focused ultrashort pulses which are delivered through a disposable applanation lens while fixating the eye under very low vacuum. VI. ALTERNATIVE PRACTICES AND PROCEDURES Alternative methods of correcting of visual correction include: glasses, contact lenses, conventional LASIK, photorefractive keratectomy and incisional cornea surgeries. Each alternative has its own advantages and disadvantages. A prospective patient should fully discuss with his/her care provider these alternatives in order to select the correction method that best meets his/her expectation and lifestyle. VII. MARKETING HISTORY The *iDesign Advanced WaveScan Studio* system is currently approved in the United States for wavefront-guided laser assisted in situ keratomileusis (LASIK) in patients with myopia. The *iDesign Advanced WaveScan Studio* system is marketed in approximately 40 countries including; Algeria, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Denmark, Egypt, Finland, France, Germany, Great Britain, India, Indonesia, Iraq, Ireland, Italy, Japan, Jordan, Malaysia, Mexico, the Netherlands, New Zealand, Poland, Qatar, Singapore, Saudi Arabia, South Africa, South Korea, Spain, Taiwan, Tunisia, Turkey, United Arab Emirates and Yemen. The *STAR S4 IR* Excimer Laser system is on market in 70 countries. Neither device has been withdrawn from any country or market for reasons of safety or effectiveness. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 5 {5} ### VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Potential adverse reactions associated with LASIK include: loss of best spectacle corrected visual acuity (BSCVA), worsening of patient complaints such as double vision, sensitivity to bright lights, increased difficulty with night vision, fluctuations in vision, increase in intraocular pressure, corneal haze, secondary surgical intervention, corneal infiltrate or ulcer, corneal epithelial defect, corneal edema, problems associated with the flap including a lost, misplaced or misaligned flap, retinal detachment, and retinal vascular accidents. Please refer to the complete listing of adverse events and complications observed during the clinical study which are presented in Tables 8 and 9 of the Summary of Clinical Studies section. ### IX. SUMMARY OF NONCLINICAL STUDIES For a summary of nonclinical studies (excluding hazard analysis and software testing) for the STAR S4 IR Excimer Laser System, please refer to the SSED of the original PMA P930016/S44 (http://www.accessdata.fda.gov/cdrh_docs/pdf/P930016S044b.pdf). ### X. SUMMARY OF PRIMARY CLINICAL STUDY #### A. Study Design A Prospective Study to Evaluate the Safety and Effectiveness of Wavefront- Guided Lasik Correction of Mixed Astigmatic Refractive Errors with the iDesign Advanced Wavescan Studio™ System and STAR S4 IR™ Excimer Laser System, Protocol STAR-112-IDMA. The safety and effectiveness of wavefront-guided LASIK correction of mixed astigmatic refractive errors with the iDesign Advanced WaveScan Studio System and STAR S4 IR Excimer Laser System has been evaluated in a clinical investigation. The study is a 2 year, prospective, multicenter, open-label, non- randomized clinical investigation of up to 150 treated eyes (of up to 200 subjects). The study is currently ongoing at seven (7) active sites in the U.S. Enrollment was closed with a total of 149 eyes of 84 subjects enrolled and treated. All subjects have completed the 3 month study visit which has been determined to be the time point of refractive stability and thus the critical time point for analysis for the PMA supplement submission. #### 1. Clinical Inclusion and Exclusion Criteria Subjects who agreed to participate provided informed consent and underwent the required screening procedures to determine eligibility. To qualify for enrollment, subjects were to meet all eligibility criteria for each eye. In general, eyes were to be healthy with iDesign Advanced WaveScan Studio system measured mixed astigmatic refractive error where the magnitude of the cylinder (up to 6.0 D) is PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 6 {6} greater than the magnitude of sphere, and the cylinder and sphere have opposite signs. # i. Subject Inclusion Criteria - At least 18 years of age and give written informed consent. The refractive error, based on the iDesign-displayed refraction selected for treatment ("4.0 Rx calc" at 12.5 mm), must be mixed astigmatism where the magnitude of cylinder (up to 6.0 D) is greater than the magnitude of sphere, and the cylinder and sphere have opposite signs. - Anticipated postoperative stromal bed thickness of at least 250 microns. - BSCVA of 20/20 or better. - Difficulty maintaining UCVA of 20/40 or better (original) or UCVA of 20/32 or worse (modified during the study), with the need for contact lens or glasses. - Less than or equal to 0.75 D difference between cycloplegic and manifest refraction sphere. - A stable refractive error over the last 12 months as defined by a change of ≤1.00 D in sphere or cylinder. - Demonstration of refractive stability for subjects who wear contact lenses: rigid or toric lenses must be removed for at least 3 weeks and soft contact lenses for a least 1 week prior to the first refraction to establish stability. - Agreement between manifest refraction (adjusted for optical infinity) and iDesign Advanced WaveScan Studio System refraction chosen for treatment. # ii. Subject Exclusion Criteria - Women who are pregnant, breast-feeding, or intend to become pregnant over the course of the study, as determined by verbal inquiry. - Concurrent use of systemic (including inhaled) medications that may impair healing (e.g., corticosteroids). - History of any of the following medical conditions, or any other condition that could affect wound healing: collagen vascular disease, autoimmune disease, immunodeficiency diseases, ocular herpes zoster or herpes simplex, endocrine disorders (including, but not limited to, unstable thyroid disorders and diabetes), lupus, rheumatoid arthritis, and diabetes (regardless of type, duration, severity or control). - Subjects with a cardiac pacemaker, implanted defibrillator or other implanted electronic device. - History of prior intraocular or corneal surgery (including cataract extraction), active ophthalmic disease or abnormality (including, but not limited to, symptomatic blepharitis, recurrent corneal erosion, dry eye syndrome, neovascularization > 1 mm from limbus), retinal detachment/repair, clinically significant lens opacity, clinical evidence of PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 7 {7} trauma, corneal opacity within the central 9 mm and visible on topography, at risk for developing strabismus, or with evidence of glaucoma or propensity for narrow angle glaucoma. - Evidence of keratoconus, corneal dystrophy or irregularity, or abnormal topography. ## 2. Follow-up Schedule and Study Procedures All eyes were evaluated according to the schedule below. Clinical Study Visit Schedule | EXAM | VISIT WINDOW | | --- | --- | | Preoperative Evaluation | | | Operative | 1-120 days following preoperative exam | | 1 Day Postoperative Exam | 12-26 hours postoperative | | 1 Week Postoperative Exam | 5-9 days postoperative | | 1 Month Periodic Exam | 3-5 weeks postoperative | | 3 Months Periodic Exam | 10-14 weeks postoperative | | 6 Months Periodic Exam | 21-26 weeks postoperative | | 9 Months Periodic Exam | 35-43 weeks postoperative | | 12 Months Periodic Exam | 11-14 months postoperative | | 24 Months Periodic Exam | 23-27 months postoperative | Study procedures included uncorrected distance visual acuity, best spectacle corrected distance visual acuity, contrast sensitivity, manifest refraction, cycloplegic refraction, keratometry, intraocular pressure, corneal pachymetry, corneal topography, *iDesign Advanced WaveScan Studio* System measurements, slit-lamp evaluation of the anterior segment, subjective questionnaires, and determination of adverse events and complications. Treatment plans were based on preoperative *iDesign Advanced WaveScan Studio* system measurements and all eyes were targeted for emmetropia. ## 3. Clinical Study Endpoints The key safety and effectiveness endpoint targets, evaluated at the time of refractive stability, are: ### i. Safety Endpoint Targets a) PRIMARY: <5% of eyes with a loss of >2 lines of best spectacle corrected visual Acuity (BSCVA) PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 8 {8} b) <1% of eyes with a BSCVA of 20/20 or better preoperatively that have a BSCVA of worse than 20/40 (Note: All eyes had to have BSCVA of 20/20 or better for study inclusion.) c) <5% of eyes with induced manifest refractive astigmatism >2.00 D (diopters) d) <1% of eyes with an adverse event (serious, non-flap related) # ii. Effectiveness Endpoint Targets a) PRIMARY: 85% of eyes with an uncorrected visual acuity (UCVA) of 20/40 or better b) 50% of eyes with a manifest refractive spherical equivalent (MRSE) within 0.50 D of intended correction. c) 75% of eyes with an MRSE within 1.00 D of intended correction d) 95% of eyes achieve refractive stability Other endpoints included contrast sensitivity, higher order aberrations, complications, visual symptoms, visual functioning and well-being, keratometric analyses, and vector and non-vector analyses of manifest refractive cylinder. The key outcome variables were assessed postoperatively at the periodic exams. Refractive stability was achieved at 3 months and confirmed at the 6 month visit; therefore, the key safety and effectiveness study endpoints were evaluated at 3 months as the primary study analysis. No retreatments were performed in the study. Therefore, no safety or effectiveness data are available for the use of the iDesign Advanced WaveScan Studio System and STAR S4 IR Excimer Laser System in performing a retreatment procedure. # iii. Statistical Methods Descriptive statistics (including sample size (n), mean, standard deviation (SD), minimum, maximum, as appropriate) and frequency distributions were used to summarize clinical outcomes. Statistical tests and resulting p-values were reported as two-sided and assessed at a 0.05 significance level. For analysis of refractive outcomes, the sphere component of the manifest refraction (as tested at 4.0 m) was adjusted for optical infinity by adding -0.25 D to the sphere magnitude. Similarly, manifest refraction spherical PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 9 {9} equivalent (MRSE) was calculated using the adjusted manifest sphere value. Additionally, all refractions were converted to plus cylinder format and adjusted for vertex distance (12.5 mm). # **B. Accountability of PMA Cohort** Eighty four (84) subjects had one or both eyes treated for a total of 149 treated eyes across 7 active clinical sites in the U.S. The majority of subjects were bilaterally treated; 65 subjects (77.4%; 65/84) had both eyes treated, and nineteen subjects (22.6%; 19/84) had a single eye treated. **Table 1** presents the accountability to date for the 149 eyes treated in this study. Subject compliance was excellent; as of database closure on June 6, 2016, all 1 and 3 month visits have been completed with percent accountability rates of 98.0% (146/149) at 1 month, and 100% (149/149) at 3 months. The study is ongoing; 64.4% (96/149) of eyes have completed the 6-month study visit, 59.7% (89/149) of eyes have completed the 9 month visit, 59.1% (88/149) of eyes have completed the 12 month visit, and 46.3% (69/149) of eyes have completed the 24 month visit. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 10 {10} **Accountability of All Treated Eyes (N=149)** | Subject Status | 1 Day | | 1 Week | | 1 Month | | 3 Months | | 6 Months | | 9 Months | | 12 Months | | 24 Months | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | **Available for Analysis** | | | | | | | | | | | | | | | | | | - In Interval (included in analysis) | 149 | 100 | 149 | 100 | 146 | 98.0 | 149 | 100 | 96 | 64.4 | 89 | 59.7 | 88 | 59.1 | 69 | 46.3 | | - Out of Interval (included in analysis) | 149 | 100 | 147 | 98.7 | 146 | 98.0 | 149 | 100 | 94 | 63.1 | 89 | 59.7 | 85 | 57.0 | 68 | 45.6 | | | 0 | 0.0 | 2 | 1.3 | 0 | 0.0 | 0 | 0.0 | 2 | 1.3 | 0 | 0.0 | 2 | 1.3 | 1 | 0.7 | | **Missing Eyes** | | | | | | | | | | | | | | | | | | - Discontinued | 0 | 0.0 | 0 | 0.0 | 3 | 2.0 | 0 | 0.0 | 3 | 2.0 | 4 | 2.7 | 6 | 4.0 | 17 | 11.4 | | - Missed visit | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | - Not seen but accounted for | 0 | 0.0 | 0 | 0.0 | 3 | 2.0 | 0 | 0.0 | 1 | 0.7 | 2 | 1.3 | 1 | 0.7 | 0 | 0.0 | | - Lost-to-follow-up | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 1.3 | 2 | 1.3 | 5 | 3.4 | 17 | 11.4 | | **Active** | | | | | | | | | | | | | | | | | | - Active (not yet in visit interval) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 50 | 33.6 | 56 | 37.6 | 56 | 37.6 | 63 | 42.3 | | - In interval or past interval (form not yet) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 32 | 21.5 | 56 | 37.6 | 56 | 37.6 | 60 | 40.3 | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 18 | 12.1 | 0 | 0.0 | 0 | 0.0 | 3 | 2.0 | | Percent Accountability^{a} (ANSI Z80.11-2012) | 100% | | 100% | | 98% | | 100% | | 97.0% | | 95.7% | | 94.6% | | 80.2% | | | ^{a} Percent Accountability = (Available for Analyses x 100) / (Enrolled [treated] – Discontinued – Active) | | | | | | | | | | | | | | | | | PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 11 {11} ### C. Study Population Demographics and Baseline Parameters Subject demographics are presented in **Table 2**. The mean age was 36.3 years (SD 10.4 years) and the majority of subjects were Caucasian (86.9%; 73/84). There were more males (53.6%; 45/84) than females (46.4%; 39/84). Most subjects (79.8%; 67/84) did not wear contact lenses preoperatively; the remaining subjects (20.2%; 17/84) wore rigid or toric contact lenses preoperatively. **Demographic Characteristics** | Category | Classification | All Subjects (N=84) | | --- | --- | --- | | | | n (%) | | Gender | Male | 45 (53.6%) | | | Female | 39 (46.4%) | | Race | Caucasian | 73 (86.9%) | | | Black/African Descent | 5 (6.0%) | | | Native American/Inuit | 1 (1.2%) | | | Asian | 2 (2.4%) | | | Pacific Islander | 0 (0.0%) | | | Other^{a} | 3 (3.6%) | | Age (Years) | Mean | 36.3 | | | SD | 10.36 | | | Min | 18 | | | Max | 58 | | Contact Lens History | No | 67 (79.8%) | | | Soft | 0 (0.0%) | | | Rigid/Toric | 17 (20.2%) | $^{a}$ Other race includes Part Filipino, Middle Eastern and Hispanic. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 12 {12} Table 3 presents the mean preoperative manifest and *iDesign Advanced WaveScan Studio* system measured refractive error for the 149 treated eyes. Mean preoperative refractive measurements were comparable between manifest refraction and *iDesign Advanced WaveScan Studio* system refraction. **Mean Preoperative Manifest and iDesign AWS Refractive Errors in Diopters** | Refractive Variable | Mean | Std Dev | Median | Min | Max | | --- | --- | --- | --- | --- | --- | | Manifest Refraction Spherical Equivalent | -0.58 | 0.84 | -0.75 | -2.38 | 2.00 | | Manifest Refractive Cylinder (MRC) | 2.99 | 1.16 | 2.75 | 0.75 | 6.00 | | iDesign Spherical Equivalent (IDSE) | -0.43 | 0.83 | -0.52 | -2.28 | 2.27 | | iDesign Refractive Cylinder (IDC) | 2.99 | 1.14 | 2.72 | 0.87 | 5.80 | Tables 4 and 5 present the preoperative refractive error bin distributions for the study population based on preoperative *iDesign Advanced WaveScan Studio* system measurements. ≥ **Preoperative Refractive Error Stratified by iDesign AWS Sphere and Cylinder** | iDesign Sphere | >1 to <=2 D^{a} | >2 to <=3 D | >3 to <=4 D | >4 to <=5 D | >5 to <=6 D | Total | | --- | --- | --- | --- | --- | --- | --- | | | N | N | N | N | N | N | | <=0 to >=-1 D | 10 | 10 | 6 | 4 | 0 | 30 | | <-1 to >=-2 D | 16 | 31 | 6 | 1 | 1 | 55 | | <-2 to >=-3 D | 0 | 22 | 14 | 4 | 1 | 41 | | <-3 to >=-4 D | 0 | 0 | 4 | 8 | 4 | 16 | | <-4 to >=-5 D | 0 | 0 | 0 | 3 | 4 | 7 | | **Total** | **26** | **63** | **30** | **20** | **10** | **149** | $^{a}$ Includes one eye with iDesign Cylinder &lt;1D (0.87 D) **Treatment of diopter ranges indicated by shaded rows and columns is locked out by AMO Treatment Card** Note: % Percentage is calculated by dividing the n(bin)/N(149). PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 13 {13} **TABLE 5** Preoperative Refractive Error Stratified by iDesign AWS Spherical Equivalent (SE) and Cylinder, All Eyes (N=149) | iDesign SE | >1 to <=2 D^{a} | >2 to <=3 D | >3 to <=4 D | >4 to <=5 D | >5 to <=6 D | Total | | --- | --- | --- | --- | --- | --- | --- | | | N | N | N | N | N | N | | >1 D | 0 | 0 | 5 | 4 | 1 | 10 | | >0 to <= 1 D | 5 | 13 | 6 | 1 | 0 | 25 | | <=0 to >=-1 D | 21 | 39 | 12 | 6 | 4 | 82 | | <-1 to >=-2 D | 0 | 11 | 7 | 7 | 4 | 29 | | <-2 to >=-3 D | 0 | 0 | 0 | 2 | 1 | 3 | | <-3 to >=-4 D | 0 | 0 | 0 | 0 | 0 | 0 | | <-4 to >=-5 D | 0 | 0 | 0 | 0 | 0 | 0 | | **Total** | **26** | **63** | **30** | **20** | **10** | **149** | $^{a}$ Includes one eye with iDesign Cylinder <1D (0.87 D) **Treatment of diopter ranges indicated by shaded rows and columns is locked out by *AMO* Treatment Card** Note: % Percentage is calculated by dividing the n(bin)/N(149). **D. Safety and Effectiveness Results** As refractive stability was achieved at 3 months, and confirmed at 6 months, the key safety and effectiveness study endpoints were evaluated at 3 months for all treated eyes (N = 149). 1. Safety Results A summary of key safety variables over time is presented in **Table 6** for all eyes. a) *Less than 5% of eyes with a loss of >2 lines BSCVA*: At 3 months, no eyes (0.0%; 0/149) had a decrease in BSCVA of >2 lines meeting the primary study endpoint safety target of <5% of eyes with a loss of >2 lines of BSCVA. b) *Less than 1% of eyes with a BSCVA of 20/20 or better preoperatively that have a BSCVA of worse than 20/40*: No eyes (0%; 0/149) had preoperative BSCVA of 20/20 or better but worse than 20/40 postoperatively at 3 months or any time during the study, meeting the safety endpoint target of <1% of eyes with preoperative BSCVA of 20/20 or better having BSCVA worse than 20/40 postoperatively. c) *Less than 5% of eyes with induced manifest refractive astigmatism >2.00 diopters*: At 3 months, no eyes (0%; 0/149) had induced manifest refractive astigmatism >2.00 D, meeting the safety criterion of <5% of eyes with induced manifest refractive astigmatism >2.00 D. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 14 {14} **Key Safety Variables Over Time** | Safety Variable | 1 Week (n=149) | | 1 Month (n=146) | | 3 Months (n=149) | | 6 Months (n=96) | | 9 Months (n=89) | | 12 Months (n=88) | | 24 Months (n=69) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | Loss of > 2 lines BSCVA^{a} | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Loss of ≥ 2 lines BSCVA | 0 | 0.0% | 1 | 0.7% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | BSCVA worse than 20/25 | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | BSCVA worse than 20/40^{b} | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Induced Manifest Cylinder >2.0 D^{c} | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | $^{a}$ **Safety endpoint target:** &lt;5% of eyes with loss of &gt;2 lines BSCVA vs. preoperative $^{b}$ **Safety endpoint target:** &lt;1% of eyes with BSCVA of 20/20 or better preoperative have BSCVA of worse than 20/40 postoperative. All eyes had preoperative BSCVA of 20/20 or better. $^{c}$ **Safety endpoint target:** &lt;5% of eyes with induced manifest refractive astigmatism &gt;2.00 D % = n/N (100) Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per time period. # d) *BSCVA Preservation* The change in lines of BSCVA postoperatively compared to preoperatively for all eyes is presented in **Table 7**. At 3 months, 42.3% (63/149) of eyes had at least a one (1) line improvement in BSCVA compared to preoperatively. No eyes were reported with a loss of &gt;2 lines of BSCVA at any visit (scheduled or unscheduled). PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 15 {15} **Change in BSCVA Over Time vs. Preoperative** | Acuity Change | 1 Week | | 1 Month | | 3 Months | | 6 Months | | 9 Months | | 12 Months | | 24 Months | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | N | % | n | % | n | % | n | % | n | % | n | % | | >2 line increase | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 1.4% | | 2 line increase | 5 | 3.4% | 6 | 4.1% | 13 | 8.7% | 11 | 11.5% | 16 | 18.0% | 8 | 9.1% | 5 | 7.2% | | 1 line increase | 39 | 26.2% | 54 | 37.0% | 50 | 33.6% | 43 | 44.8% | 39 | 43.8% | 44 | 50.0% | 36 | 52.2% | | No change | 90 | 60.4% | 80 | 54.8% | 82 | 55.0% | 38 | 39.6% | 32 | 36.0% | 33 | 37.5% | 24 | 34.8% | | 1 line decrease | 15 | 10.1% | 5 | 3.4% | 4 | 2.7% | 4 | 4.2% | 2 | 2.2% | 3 | 3.4% | 3 | 4.3% | | 2 line decrease | 0 | 0.0% | 1 | 0.7% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | >2 line decrease | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | All | 149 | | 146 | | 149 | | 96 | | 89 | | 88 | | 69 | | Percentage calculated based on non-missing values. % = n/N (100) Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per time period. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 16 {16} # e) Adverse Events A summary of adverse events (following the ANSI Guidance Document for Corneal Reshaping, Z80.11-2012) is presented in **Table 8**. There were no occurrences of the ANSI-specific adverse events in this study (0%, 0/149). There was one case of non-serious, device-related TLSS (0.7%; 1/149) which resolved within 1 month. One (1) additional eye (0.7%; 1/149) experienced two (2) complications (trace DLK and epithelial ingrowth) which required treatment during the first month and these events were classified as non-serious, device-related adverse events. Thus, a total of two (2) eyes (1.3%; 2/149) experienced non-serious, device-related adverse events in this study. *Less than 1% of eyes with an adverse event (serious, non-flap related):* No serious ocular adverse events have been reported in this study (0%; 0/149). As such, the safety criterion for the overall rate of serious, non-flap related, adverse events (< 1%) was achieved. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 17 {17} **TABLE 8** **Summary of Adverse Events Over Time; All Eyes (N=149)** | Complication | < 1 Month (n=149) | | 1 Month (n=146) | | 3 Months (n=149) | | 6 Months (n=96) | | 9 Months (n=89) | | 12 Months (n=88) | | 24 Months (n=69) | | Cumulative (n=149) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | Corneal infiltrate or ulcer | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Any persistent corneal epithelial defect at 1 month or later | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Corneal edema at 1 month or later (specify "flap", "bed", or both) | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Epithelium in the interface with loss of 2 lines (≥10 letters) or more of BSCVA | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Miscreated flap (decentered, lost, incomplete, too thin, or other) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Melting of the flap | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | IOP with increase >10 mmHg above baseline on two consecutive examinations or an IOP >30 mmHg on two consecutive examinations | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Haze beyond 6 months with loss of 2 lines or greater (≥10 letters) | | | | | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Ocular penetration | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Severe glare, dry eye, or halos at 3 months or later | | | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Decrease in BSCVA of greater than or equal to 2 lines (≥10 letters) not due to irregular astigmatism, at 3 months or later | | | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Any other vision-threatening event | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Diffuse Lamellar Keratitis (DLK, grade 3 or above) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Retinal detachment | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Retinal vascular accidents | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Other adverse events: | | | | | | | | | | | | | | | | | | Transient Light Sensitivity Syndrome | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | | Trace diffuse lamellar keratitis (DLK) requiring extended treatment | 1^{a} | 0.7 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1^{a} | 0.7 | | Epithelial ingrowth requiring removal | 1^{a} | 0.7 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1^{a} | 0.7 | Shaded areas represent time frames outside event definition $^{a}$ Same eye. Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per time period. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 18 {18} # f) *Complications* Complications that occurred during the study are presented in **Table 9**. Complications are defined as anticipated, transient, and non-sight-threatening events. There were no reports of corneal epithelial defects or diffuse lamellar keratitis (DLK; grade 2 or less) at 1 month or later. There were reports of epithelium in the interface (epithelial ingrowth) over time (4.0% at 3 months) but all were either trace or mild in severity (further details in Section 7.4.5, Anterior Segment Evaluation). There were also reports of foreign body sensation and pain at 1 month or later (7.4 % and 2.0% at 3 months, respectively) but most of these were reported as mild. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 19 {19} **Summary of Complications Over Time** | Complication | | <1 Month (n=149) | | 1 Month (n=146) | | 3 Months (n=149) | | 6 Months (n=96) | | 9 Months (n=89) | | 12 Months (n=88) | | 24 Months (n=69) | | Cumulative (n=149) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | Corneal edema between 1 week and 1 month after procedure | Total^{a} | 0 | 0.0 | | | | | | | | | | | | | | | | | Cornea | 0 | 0.0 | | | | | | | | | | | | | | | | | Flap | 0 | 0.0 | | | | | | | | | | | | | | | | Peripheral corneal epithelial defect at 1 month or later (location of defect to be identified as on, off, or across the flap) | | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | | 0 | 0.0 | | Epithelium in the interface (epithelial ingrowth; trace/mild) | Total^{a} | 2 | 1.3 | 5 | 3.4 | 6 | 4.0 | 5 | 5.2 | 4 | 4.5 | 3 | 3.4 | 1 | 1.4 | 8 | 5.4 | | | Cornea | 2 | 1.3 | 5 | 3.4 | 5 | 3.4 | 4 | 4.2 | 3 | 3.4 | 3 | 3.4 | 1 | 1.4 | 7 | 4.7 | | | Flap | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | 1 | 1.0 | 1 | 1.1 | 0 | 0.0 | 0 | 0.0 | 1 | 0.7 | | Diffuse Lamellar Keratitis (DLK, Grade 2 or less) | Total^{a} | 3^{b} | 2.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 3^{b} | 2.0 | | | Cornea | 3^{b} | 2.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 3^{b} | 2.0 | | | Flap | 0^{b} | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Foreign body sensation at 1 month or later | | | | 17^{c} | 11.6 | 11^{c} | 7.4 | 2^{c} | 2.1 | 5^{c} | 5.6 | 3^{c} | 3.4 | 1^{c} | 1.4 | 22^{c} | 14.8 | | Pain at 1 month or later | | | | 5^{d} | 3.4 | 3^{d} | 2.0 | 4^{d} | 4.2 | 0 | 0.0 | 4^{d} | 4.5 | 5^{d} | 7.2 | 17^{d} | 11.4 | Shaded areas represent time frames outside complication definition. $^{a}$ Finding noted on cornea and flap; no duplicate reports at the same visit. $^{b}$ All reports of DLK were Grade 2 (mild) or less. $^{c}$ Most reports were mild; 6 moderate reports at 1 month. All reports at 3, 6, 9, 12, and 24 months were mild. No marked or severe reports. $^{d}$ Most reports were mild; 1 moderate report at 1 month, 2 moderate reports at 3 months, and 1 moderate report at 24 months. All reports at 6, 9, 12, and 24 months were mild. No marked or severe reports. Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per time period. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 20 {20} # g) *Directed Visual Symptoms* **Table 10** presents subjective visual symptoms at preoperative, 3 months and 6 months from the “directed symptom assessment” as reported by subjects when specifically queried about each symptom at study visits. The directed symptom assessment questionnaire was not evaluated for its ability to validly assess patient- reported visual symptoms. Reports of subjective visual symptoms were typical following LASIK refractive procedures. Preoperatively, night glare, halos and difficulty driving at night were reported with the highest severity (“Severe”). At 3 months, there were no reports of “severe” symptoms and the visual symptoms reported with the highest severity (“marked”) included photophobia, and dryness. There were no “marked” or “severe” reports at 6 months or later. Post-hoc analyses of the change in the number of reports of moderate, marked, and severe reports at 3 months vs. preoperative and at 6 months vs. preoperative (**Table 11**) showed an increase in reports of dryness (7.4% at 3 months; 6.3% at 6 months) as well as reductions in reports of photophobia (-4.2% at 6 months), day glare (-4.7% at 3 months; -6.3% at 6 months), night glare (-10.7% at 3 months; -16.7% at 6 months,), halos (-10.7% at 3 months; -12.5% at 6 months), and driving at night (-15.4% at 3 months; -25.0% at 6 months). PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 21 {21} **TABLE 10** **Directed Visual Symptoms at Preoperative, 3 Months, and 6 Months** **All Eyes (N=149)** | Symptom | Visit | None | | Mild | | Moderate | | Marked | | Severe | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | n | % | n | % | n | % | n | % | n | % | | Pain | Preop | 138 | 92.6% | 11 | 7.4% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 146 | 98.0% | 1 | 0.7% | 2 | 1.3% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 92 | 95.8% | 4 | 4.2% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Tearing | Preop | 127 | 85.2% | 22 | 14.8% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 140 | 94.0% | 7 | 4.7% | 2 | 1.3% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 92 | 95.8% | 4 | 4.2% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Photophobia | Preop | 132 | 88.6% | 13 | 8.7% | 3 | 2.0% | 1 | 0.7% | 0 | 0.0% | | | 3 Months | 118 | 79.2% | 26 | 17.4% | 4 | 2.7% | 1 | 0.7% | 0 | 0.0% | | | 6 Months | 82 | 85.4% | 14 | 14.6% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Foreign Body Sensation | Preop | 147 | 98.7% | 2 | 1.3% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 138 | 92.6% | 11 | 7.4% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 94 | 97.9% | 2 | 2.1% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Dryness | Preop | 100 | 67.1% | 44 | 29.5% | 5 | 3.4% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 76 | 51.0% | 57 | 38.3% | 14 | 9.4% | 2 | 1.3% | 0 | 0.0% | | | 6 Months | 42 | 43.8% | 43 | 44.8% | 11 | 11.5% | 0 | 0.0% | 0 | 0.0% | | Fluctuation of Vision | Preop | 120 | 80.5% | 26 | 17.4% | 3 | 2.0% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 105 | 70.5% | 39 | 26.2% | 5 | 3.4% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 74 | 77.1% | 22 | 22.9% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Day Glare | Preop | 112 | 75.2% | 30 | 20.1% | 6 | 4.0% | 1 | 0.7% | 0 | 0.0% | | | 3 Months | 137 | 91.9% | 12 | 8.1% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 83 | 86.5% | 12 | 12.5% | 1 | 1.0% | 0 | 0.0% | 0 | 0.0% | | Night Glare | Preop | 87 | 58.4% | 43 | 28.9% | 16 | 10.7% | 2 | 1.3% | 1 | 0.7% | | | 3 Months | 106 | 71.1% | 40 | 26.8% | 3 | 2.0% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 73 | 76.0% | 22 | 22.9% | 1 | 1.0% | 0 | 0.0% | 0 | 0.0% | | Binocular Diplopia | Preop | 147 | 98.7% | 0 | 0.0% | 2 | 1.3% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 145 | 97.3% | 4 | 2.7% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 96 | 100.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Monocular Diplopia | Preop | 147 | 98.7% | 2 | 1.3% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 147 | 98.7% | 2 | 1.3% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 96 | 100.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Ghosting | Preop | 143 | 96.0% | 4 | 2.7% | 2 | 1.3% | 0 | 0.0% | 0 | 0.0% | | | 3 Months | 142 | 95.3% | 6 | 4.0% | 1 | 0.7% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 89 | 92.7% | 7 | 7.3% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Halos | Preop | 74 | 49.7% | 55 | 36.9% | 18 | 12.1% | 1 | 0.7% | 1 | 0.7% | | | 3 Months | 86 | 57.7% | 59 | 39.6% | 4 | 2.7% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 64 | 66.7% | 28 | 29.2% | 4 | 4.2% | 0 | 0.0% | 0 | 0.0% | | Difficulty Driving at Night | Preop | 75 | 50.3% | 46 | 30.9% | 25 | 16.8% | 2 | 1.3% | 1 | 0.7% | | | 3 Months | 122 | 81.9% | 22 | 14.8% | 5 | 3.4% | 0 | 0.0% | 0 | 0.0% | | | 6 Months | 79 | 82.3% | 17 | 17.7% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | Note: The non-shaded areas indicate reports of visual symptoms. Note: Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 22 {22} **Changes in Moderate/Marked/Severe Visual Symptoms vs. Preoperative** | Symptoms | Preoperative | | | | 3 Months | | | | Difference^{a} in Moderate, Marked & Severe Symptoms | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | None & Mild | | Moderate, Marked & Severe | | None & Mild | | Moderate, Marked & Severe | | | | | n | % | n | % | n | % | n | % | | | Pain Tearing | 149 | 100.0% | 0 | 0.0% | 147 | 98.7% | 2 | 1.3% | 1.3% | | Photophobia | 149 | 100.0% | 0 | 0.0% | 147 | 98.7% | 2 | 1.3% | 1.3% | | Foreign Body Sensation | 145 | 97.3% | 4 | 2.7% | 144 | 96.6% | 5 | 3.4% | 0.7% | | Dryness Vision | 149 | 100.0% | 0 | 0.0% | 149 | 100.0% | 0 | 0.0% | 0.0% | | Fluctuation Day | 144 | 96.6% | 5 | 3.4% | 133 | 89.3% | 16 | 10.7% | 7.4% | | Glare | 146 | 98.0% | 3 | 2.0% | 144 | 96.6% | 5 | 3.4% | 1.3% | | Night Glare | 142 | 95.3% | 7 | 4.7% | 149 | 100.0% | 0 | 0.0% | -4.7% | | Binocular Diplopia | 130 | 87.2% | 19 | 12.8% | 146 | 98.0% | 3 | 2.0% | -10.7% | | Monocular Diplopia | 147 | 98.7% | 2 | 1.3% | 149 | 100.0% | 0 | 0.0% | -1.3% | | Ghosting | 149 | 100.0% | 0 | 0.0% | 149 | 100.0% | 0 | 0.0% | 0.0% | | Halos | 147 | 98.7% | 2 | 1.3% | 148 | 99.3% | 1 | 0.7% | -0.7% | | Driving at night | 129 | 86.6% | 20 | 13.4% | 145 | 97.3% | 4 | 2.7% | -10.7% | | | 121 | 81.2% | 28 | 18.8% | 144 | 96.6% | 5 | 3.4% | -15.4% | $^{a}$ Difference= 3 months minus preoperative Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes (149). **At 6 Months: All Eyes (N= 96)** | Symptoms | Preoperative | | | | 6 Months | | | | Difference^{a} in Moderate, Marked & Severe Symptoms | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | None & Mild | | Moderate, Marked & Severe | | None & Mild | | Moderate, Marked & Severe | | | | | n | % | n | % | n | % | n | % | | | Pain Tearing | 96 | 100.0% | 0 | 0.0% | 96 | 100.0% | 0 | 0.0% | 0.0% | | Photophobia | 96 | 100.0% | 0 | 0.0% | 96 | 100.0% | 0 | 0.0% | 0.0% | | Foreign Body Sensation | 92 | 95.8% | 4 | 4.2% | 96 | 100.0% | 0 | 0.0% | -4.2% | | Dryness Vision | 96 | 100.0% | 0 | 0.0% | 96 | 100.0% | 0 | 0.0% | 0.0% | | Fluctuation Day | 91 | 94.8% | 5 | 5.2% | 85 | 88.5% | 11 | 11.5% | 6.3% | | Glare | 93 | 96.9% | 3 | 3.1% | 96 | 100.0% | 0 | 0.0% | -3.1% | | Night Glare | 89 | 92.7% | 7 | 7.3% | 95 | 99.0% | 1 | 1.0% | -6.3% | | Binocular Diplopia | 79 | 82.3% | 17 | 17.7% | 95 | 99.0% | 1 | 1.0% | -16.7% | | Monocular Diplopia | 96 | 100.0% | 0 | 0.0% | 96 | 100.0% | 0 | 0.0% | 0.0% | | Ghosting | 96 | 100.0% | 0 | 0.0% | 96 | 100.0% | 0 | 0.0% | 0.0% | | Halos | 94 | 97.9% | 2 | 2.1% | 96 | 100.0% | 0 | 0.0% | -2.1% | | Driving at night | 80 | 83.3% | 16 | 16.7% | 92 | 95.8% | 4 | 4.2% | -12.5% | | | 72 | 75.0% | 24 | 25.0% | 96 | 100.0% | 0 | 0.0% | -25.0% | $^{b}$ Difference= 3 months minus preoperative Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes (96). PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 23 {23} # h) *Contrast Sensitivity* Monocular best corrected distance contrast sensitivity was evaluated preoperatively and postoperatively at 3, 6, and 12 months under mesopic (3 cd/m²) conditions with and without glare and photopic (85 cd/m²) conditions without glare at 4 spatial frequencies (3, 6, 12, and 18 cycles per degree, cpd). As shown in **Table 12**, at 3 months, under all three lighting conditions, the mean changes in contrast sensitivity were all positive indicating an increase in contrast sensitivity postoperatively, and nearly all were statistically significant after adjusting for multiplicity (**p≤0.036**). Statistically significant improvements under all lighting conditions were found at the 12 cpd spatial frequency (**p<0.0001**) with mean changes of up to 0.17 log units. Additionally, there were statistically significant improvements at the 6 cpd spatial frequency under mesopic conditions with and without glare conditions (**p≤0.007**) and at the 18 cpd spatial frequency under photopic and mesopic without glare condition (**p≤0.006**). **Table 13** presents the number of eyes unable to see the reference patterns at each spatial frequency and lighting condition at preoperative and 3,6,12 and 24 months. At 3 months, there were fewer eyes that were unable to see the reference patterns (up to 2.7%) compared to preoperatively (up to 8.1%). As shown in **Table 14**, most eyes (≥90%) had either no change or clinically significant improvements in contrast sensitivity (0.30 log units or more at two or more spatial frequencies) under all lighting conditions at 3 months vs. preoperative. Under all lighting conditions, there was approximately a three-fold increase in the proportions of eyes with clinically significant increases (14.8% to 30.2%) compared to decreases (4.7% to 8.7%) at 3 months. Overall, there were positive changes in mean contrast sensitivity postoperatively and most eyes experiencing either no change or an improvement in contrast sensitivity postoperatively compared to preoperatively. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 24 {24} TABLE 12 Mean Change in Contrast Sensitivity at 3,6,12 and 24 Months From Preoperative All Eyes (N=149) | | Preoperative (n=149) | | | | Change from Preoperative to 3 months (n=149) | | | | Change from Preoperative to 6 months (n=96) | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Lighting Condition | 3 cpd | 6 cpd | 12 cpd | 18 cpd | 3 cpd | 6 cpd | 12 cpd | 18 cpd | 3 cpd | 6 cpd | 12 cpd | 18 cpd | | Photopic w/o Glare | | | | | | | | | | | | | | Mean (Log units) | 1.71 | 1.94 | 1.59 | <1.13 | 0.03 | 0.04 | 0.09 | >0.07 | 0.06 | 0.06 | 0.10 | 0.12 | | SE P-Value | 0.015 | 0.016 | 0.024 | >0.023 | 0.015 | 0.016 | 0.023 | >0.022 | 0.018 | 0.022 | 0.033 | 0.031 | | Adjusted P-value | - | - | - | - | 0.036 | 0.018 | 0.000 | 0.001 | 0.001 | 0.011 | 0.002 | 0.000 | | | | | | | 0.075 | 0.072 | 0.000 | 0.006 | | | | | | Mesopic w/o Glare | | | | | | | | | | | | | | Mean (Log units) | 1.64 | <1.69 | <1.22 | <0.75 | 0.04 | >0.08 | >0.13 | >0.13 | 0.07 | >0.13 | >0.16 | >0.18 | | SE | 0.016 | >0.021 | >0.031 | >0.030 | 0.019 | >0.024 | >0.033 | >0.030 | 0.024 | >0.029 | >0.041 | >0.036 | | P-Value | - | - | - | - | 0.068 | 0.001 | 0.000 | 0.000 | 0.005 | 0.000 | 0.000 | 0.000 | | Adjusted P-value | | | | | 0.075 | 0.007 | 0.000 | 0.000 | | | | | | Mesopic w/ Glare | | | | | | | | | | | | | | Mean (Log units) | 1.63 | <1.66 | <1.15 | <0.76 | 0.03 | >0.08 | >0.17 | >0.08 | 0.06 | >0.14 | >0.21 | >0.09 | | SE | 0.017 | >0.024 | >0.030 | >0.030 | 0.015 | >0.022 | >0.034 | >0.031 | 0.022 | >0.032 | >0.045 | >0.040 | | P-Value | - | - | - | - | 0.025 | 0.000 | 0.000 | 0.010 | 0.008 | 0.000 | 0.000 | 0.024 | | Adjusted P-value | | | | | 0.075 | 0.000 | 0.000 | 0.050 | | | | | | SE = standard error Positive values for 'change from preoperative' represent increase in contrast sensitivity scores. Eyes that were unable to see the reference patterns were assigned the reference pattern scores. Therefore, mean scores at preoperative may be less than (<) values and SE maybe greater than (>) values if any eyes were unable to see the reference patterns. If no eyes were unable to see the reference patterns, then means and SEs are equal to the values. Mean changes from preoperative and standard errors are greater than (>) values when more eyes were unable to see the reference patterns preoperatively than postoperatively. P-values are based on one sample t-test. P-value of 0.000 represents p-value of <0.0001. Multiplicity adjusted p-values for the change from preoperative to 3 months based on the Bonferroni step-down (Holm's step-down) method. | | | | | | | | | | | | | PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 25 {25} (continued) Mean Change in Contrast Sensitivity | | Preoperative (n=149) | | | | Change from Preoperative to 12 months (n=149) | | | | Change from Preoperative to 24 months (n=96) | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Lighting Condition | 3 cpd | 6 cpd | 12 cpd | 18 cpd | 3 cpd | 6 cpd | 12 cpd | 18 cpd | 3 cpd | 6 cpd | 12 cpd | 18 cpd | | Photopic w/o Glare | | | | | | | | | | | | | | Mean (Log units) | 1.71 | 1.94 | 1.59 | <1.13 | 0.03 | 0.07 | 0.15 | 0.13 | 0.05 | 0.01 | <0.01 | <-0.03 | | SE | 0.015 | 0.016 | 0.024 | >0.023 | 0.021 | 0.025 | 0.035 | 0.032 | 0.025 | 0.034 | >0.055 | >0.053 | | P-Value | - | - | - | - | 0.105 | 0.004 | 0.000 | 0.000 | 0.063 | 0.846 | 0.904 | 0.627 | | Adjusted P-value | | | | | | | | | | | | | | Mesopic w/o Glare | | | | | | | | | | | | | | Mean (Log units) | 1.64 | <1.69 | <1.22 | <0.75 | 0.08 | >0.17 | >0.17 | >0.17 | 0.05 | >0.18 | >0.18 | 0.14 | | SE | 0.016 | >0.021 | >0.031 | >0.030 | 0.022 | >0.030 | >0.052 | >0.045 | 0.024 | >0.035 | >0.055 | 0.054 | | P-Value | - | - | - | - | 0.001 | 0.000 | 0.001 | 0.000 | 0.052 | 0.000 | 0.002 | 0.010 | | Adjusted P-value | | | | | | | | | | | | | | Mesopic w/ Glare | | | | | | | | | | | | | | Mean (Log units) | 1.63 | <1.66 | <1.15 | <0.76 | 0.07 | >0.16 | >0.18 | >0.19 | 0.06 | >0.13 | >0.14 | <0.08 | | SE P-Value | 0.017 | >0.024 | >0.030 | >0.030 | 0.024 | >0.032 | >0.047 | >0.044 | 0.025 | >0.036 | >0.055 | >0.057 | | Adjusted P-value | - | - | - | - | 0.003 | 0.000 | 0.000 | 0.000 | 0.022 | 0.001 | 0.011 | 0.178 | | SE = standard error Positive values for 'change from preoperative' represent increase in contrast sensitivity scores. Eyes that were unable to see the reference patterns were assigned the reference pattern scores. Therefore, mean scores at preoperative may be less than (<) values and SE maybe greater than (>) values if any eyes were unable to see the reference patterns. If no eyes were unable to see the reference patterns, then means and SEs are equal to the values. Mean changes from preoperative and standard errors are greater than (>) values when more eyes were unable to see the reference patterns preoperatively than postoperatively. P-values are based on one sample t-test. P-value of 0.000 represents p-value of <0.0001. Multiplicity adjusted p-values for the change from preoperative to 3 months based on the Bonferroni step-down (Holm's step-down) method. | | | | | | | | | | | | | PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 26 {26} **Proportions of Eyes Unable to See the Contrast Sensitivity Reference Patterns at Preoperative and 3 Months** | Lighting Condition | Spatial Frequency | Preoperative | | 3 Months | | | --- | --- | --- | --- | --- | --- | | | | n | % | n | % | | Photopic without Glare | 3.0 cpd | 0 | 0.0% | 0 | 0.0% | | | 6.0 cpd | 0 | 0.0% | 0 | 0.0% | | | 12.0 cpd | 0 | 0.0% | 0 | 0.0% | | | 18.0 cpd | 1 | 0.7% | 0 | 0.0% | | Mesopic without Glare | 3.0 cpd | 0 | 0.0% | 0 | 0.0% | | | 6.0 cpd | 3 | 2.0% | 0 | 0.0% | | | 12.0 cpd | 7 | 4.7% | 1 | 0.7% | | | 18.0 cpd | 12 | 8.1% | 4 | 2.7% | | Mesopic with Glare | 3.0 cpd | 0 | 0.0% | 0 | 0.0% | | | 6.0 cpd | 4 | 2.7% | 0 | 0.0% | | | 12.0 cpd | 9 | 6.0% | 4 | 2.7% | | | 18.0 cpd | 11 | 7.4% | 4 | 2.7% | **Clinically Significant Changes$^{a}$ in Contrast Sensitivity at 3,6,12 and 24 Months from Preoperative** | | 3 Months (n=149) | | | | 6 Months (n=96) | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Decrease n % | No change n % | Increase n % | Not reported n | Decrease n % | No change n % | Increase n % | Not reported n | | Photopic without Glare | 7 4.7% | 120 80.5% | 22 14.8% | 0 | 7 7.3% | 66 68.8% | 23 24.0% | 0 | | Mesopic without Glare | 13 8.7% | 91 61.1% | 45 30.2% | 0 | 8 8.3% | 55 57.3% | 33 34.4% | 0 | | Mesopic with Glare | 11 7.4% | 101 67.8% | 37 24.8% | 0 | 9 9.4% | 61 63.5% | 26 27.1% | 0 | PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 27 {27} | | 12 Months (n=88) | | | | 24 Months (n=88) | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Decrease n % | No change n % | Increase n % | Not reported n | Decrease n % | No change n % | Increase n % | Not reported n | | Photopic without Glare | 4 4.5% | 62 70.5% | 22 25.0% | 0 | 10 14.5% | 44 63.8% | 15 21.7% | 0 | | Mesopic without Glare | 8 9.1% | 46 52.3% | 34 38.6% | 0 | 4 5.8% | 40 58.0% | 25 36.2% | 0 | | Mesopic with Glare | 7 8.0% | 44 50.0% | 37 42.0% | 0 | 9 13.0% | 36 52.2% | 24 34.8% | 0 | | Confidence Intervals calculated based on Clopper-Pearson Exact method. Percentages calculated based on non-missing values. ^{a}A difference of ≥0.30 log units from preoperative at 2 or more spatial frequencies is considered a clinically significant change in contrast sensitivity. | | | | | | | | | PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 28 {28} # i) Higher Order Aberrations As shown in Table 15, analyses of higher order aberrations (HOA) showed that HOA root mean square (RMS; absolute value) increased postoperatively, mostly associated with an increase in secondary astigmatism. Spherical aberration (signed) was reduced postoperatively. All other higher order aberration terms, on average, increased by no more than 0.01 μm with 4 mm standardized wavefront diameters. TABLE 15 Higher Order Aberrations (HOA) RMS (μm) at Preoperative and ,6,9, 12 and 24 Months with 4 mm Standardized Wavefront Diameters | | Preoperative (n=146) Mean +/- SD | 1 Month (n=139) Mean +/- SD | 3 Months (n=142) Mean +/- SD | 6 Months (n=93) Mean +/- SD | 9 Months (n=85) Mean +/- SD | 12 Months (n=84) Mean +/- SD | 24 Months (n=61) Mean +/- SD | | --- | --- | --- | --- | --- | --- | --- | --- | | HOA RMS (μm) | 0.12 +/- 0.05 | 0.15 +/- 0.08 | 0.14 +/- 0.09 | 0.14 +/- 0.07 | 0.13 +/- 0.06 | 0.13 +/- 0.07 | 0.13 +/- 0.06 | | Coma | 0.07 +/- 0.04 | 0.08 +/- 0.06 | 0.08 +/- 0.06 | 0.08 +/- 0.06 | 0.07 +/- 0.05 | 0.08 +/- 0.05 | 0.08 +/- 0.05 | | Spherical Aberration | 0.04 +/- 0.03 | 0.04 +/- 0.03 | 0.04 +/- 0.04 | 0.03 +/- 0.03 | 0.03 +/- 0.03 | 0.03 +/- 0.03 | 0.03 +/- 0.02 | | Trefoil | 0.06 +/- 0.04 | 0.07 +/- 0.05 | 0.07 +/- 0.06 | 0.07 +/- 0.05 | 0.07 +/- 0.05 | 0.07 +/- 0.04 | 0.07 +/- 0.04 | | Secondary Coma | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | | Secondary Astigmatism | 0.03 +/- 0.02 | 0.05 +/- 0.04 | 0.04 +/- 0.04 | 0.04 +/- 0.03 | 0.04 +/- 0.03 | 0.04 +/- 0.03 | 0.04 +/- 0.03 | | Secondary Spherical | 0.00 +/- 0.00 | 0.00 +/- 0.00 | 0.00 +/- 0.00 | 0.00 +/- 0.00 | 0.00 +/- 0.00 | 0.00 +/- 0.00 | 0.00 +/- 0.00 | | Tetrafoil | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | | Fifth Order | 0.01 +/- 0.01 | 0.02 +/- 0.01 | 0.02 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.02 +/- 0.01 | | Sixth Order | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | 0.01 +/- 0.01 | | Spherical Aberration | 0.03 +/- 0.03 | -0.01 +/- 0.05 | -0.01 +/- 0.05 | 0.00 +/- 0.04 | 0.00 +/- 0.04 | 0.00 +/- 0.05 | 0.01 +/- 0.04 | | iDesign Spherical Equivalent (D)a | -0.43 +/- 0.83 | 0.18 +/- 0.58 | 0.15 +/- 0.47 | 0.16 +/- 0.45 | 0.21 +/- 0.44 | 0.17 +/- 0.45 | 0.15 +/- 0.47 | | iDesign Cylinder magnitude (D)a | 2.99 +/- 1.14 | 0.51 +/- 0.30 | 0.51 +/- 0.31 | 0.55 +/- 0.27 | 0.55 +/- 0.28 | 0.58 +/- 0.29 | 0.57 +/- 0.30 | a Low order aberrations from 4.0 mm iDesign measurements collected by sites. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 29 {29} ## 2. Effectiveness Results A summary of the key effectiveness variables over time is presented in **Table 16** for all eyes. a) *85% of eyes with a UCVA of 20/40 or better:* At 3 months, UCVA of 20/40 or better was achieved in 100% (149/149) of eyes, exceeding the primary study effectiveness endpoint target of 85% of eyes with 20/40 or better UCVA. Furthermore at 3 months, 91.9% (137/149) of eyes were 20/20 or better and 57.0% (85/149) were 20/16 or better. Overall, the proportions of eyes that achieved UCVA of 20/40 or better exceeded the target rate (85%) across all postoperative study visits. b) *Proportion of eyes with an MRSE within 0.50 D and 1.00 D of intended correction:* The secondary effectiveness endpoints pertaining to the accuracy of treatment were met at 3 months with 90.6% (135/149) of eyes having MRSE within 0.50 D of emmetropia and 97.3% (145/149) within 1.00 D, exceeding the study endpoint targets of 50% within 0.50 D and 75% within 1.00 D. Additionally at 3 months, all eyes (100.0%; 149/149) had MRSE within 2.00 D. The key effectiveness variables at 3 months stratified by preoperative IDSE are presented in **Table 17**. UCVA and MRSE effectiveness endpoints were met for all preoperative IDSE groups with 100.0% of eyes achieving UCVA of 20/40 or better (target ≥85%), ≥82.8% of eyes achieving MRSE within 0.50 D (target ≥50%), and ≥89.7% of eyes achieving MRSE within 1.00 D (target ≥75%). PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 30 {30} **Key Effectiveness Variables Over Time** | Effectiveness Variable | 1 Month (n=146) | | 3 Months (n=149) | | 6 Months (n=96) | | 9 Months (n=89) | | 12 Months (n=88) | | 24 Months (n=69) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | | UCVA 20/16 or better | 74 | 50.7% | 85 | 57.0% | 61 | 63.5% | 55 | 61.8% | 55 | 62.5% | 45 | 65.2% | | UCVA 20/20 or better | 134 | 91.8% | 137 | 91.9% | 88 | 91.7% | 82 | 92.1% | 81 | 92.0% | 60 | 87.0% | | **UCVA 20/40 or better^{a}** | 145 | 99.3% | 149 | 100% | 96 | 100% | 89 | 100% | 88 | 100% | 67 | 97.1% | | **MRSE +/- 0.50 D^{b}** | 127 | 87.0% | 135 | 90.6% | 80 | 83.3% | 80 | 89.9% | 75 | 85.2% | 56 | 81.2% | | **MRSE +/- 1.00 D^{c}** | 144 | 98.6% | 145 | 97.3% | 95 | 99.0% | 87 | 97.8% | 87 | 98.9% | 66 | 95.7% | | MRSE +/- 2.00 D | 146 | 100% | 149 | 100% | 96 | 100% | 89 | 100% | 88 | 100% | 69 | 100% | $^{a}$ Study endpoint target: 85% of eyes 20/40 or better UCVA $^{b}$ Study endpoint target: 50% of eyes within 0.50 D MRSE $^{c}$ Study endpoint target: 75% of eyes within 1.00 D MRSE Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per time period. **Key UCVA and MRSE Variables at 3 Months by Preop iDesign AWS Spherical Equivalent (IDSE), All Eyes (N=149)** | Preoperative IDSE Diopter Group (n) | UCVA 20/20 or better | | UCVA 20/40 or better^{a} | | MRSE within 0.50 D^{b} | | MRSE within 1.00 D^{c} | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | | **>1 D (n=10)** | 8 | 80.0% | 10 | 100% | 9 | 90.0% | 10 | 100% | | **≤ 1 to > 0 D (n=25)** | 22 | 88.0% | 25 | 100% | 23 | 92.0% | 24 | 96.0% | | **≤ 0 to ≥ -1 D (n=82)** | 79 | 96.3% | 82 | 100% | 76 | 92.7% | 82 | 100% | | **<-1 to ≥ -2 D (n=29)** | 26 | 89.7% | 29 | 100% | 24 | 82.8% | 26 | 89.7% | | **<-2 to ≥ -3 D (n=3)** | 2 | 66.7% | 3 | 100% | 3 | 100% | 3 | 100% | | **Total (N=149)** | 137 | 91.9% | 149 | 100% | 135 | 90.6% | 145 | 97.3% | $^{a}$ Study endpoint target: 85% of eyes 20/40 or better UCVA $^{b}$ Study endpoint target: 50% of eyes within 0.50 D MRSE $^{c}$ Study endpoint target: 75% of eyes within 1.00 D MRSE Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per diopter row. The key effectiveness variables at 3 months stratified by preoperative IDC are presented in **Table 18**. UCVA and MRSE effectiveness endpoints were met PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 31 {31} for all preoperative IDC groups with 100.0% of eyes achieving UCVA of 20/40 or better (target ≥85%), ≥80.0% of eyes achieving MRSE within 0.50 D (target ≥50%), and ≥90.0% of eyes achieving MRSE within 1.00 D (target ≥75%). **TABLE 18** **Key UCVA and MRSE Variables at 3 Months** **by Preoperative iDesign AWS Cylinder (IDC)** **All Eyes (N=149)** | Preoperative IDC Diopter Group (n) | UCVA 20/20 or better | | UCVA 20/40 or better^{b} | | MRSE within 0.50 D^{c} | | MRSE within 1.00 D^{d} | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | | >1^{a} to ≤ 2 D (n=26) | 26 | 100% | 26 | 100% | 23 | 88.5% | 26 | 100% | | >2 to ≤ 3 D (n=63) | 60 | 95.2% | 63 | 100% | 59 | 93.7% | 63 | 100% | | >3 to ≤ 4 D (n=30) | 26 | 86.7% | 30 | 100% | 29 | 96.7% | 29 | 96.7% | | >4 to ≤ 5 D (n=20) | 17 | 85.0% | 20 | 100% | 16 | 80.0% | 18 | 90.0% | | >5 to ≤ 6 D (n=10) | 8 | 80.0% | 10 | 100% | 8 | 80.0% | 9 | 90.0% | | **Total (N=149)** | **137** | **91.9%** | **149** | **100%** | **135** | **90.6%** | **145** | **97.3%** | $^{a}$ Includes one eye with iDesign Cylinder <1D (0.87 D) $^{b}$ Study endpoint target: 85% of eyes 20/40 or better UCVA $^{d}$ Study endpoint target: 50% of eyes within 0.50 D MRSE $^{d}$ Study endpoint target: 75% of eyes within 1.00 D MRSE Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per diopter row. **Table 19** presents the distribution of UCVA results over time for all eyes. Postoperatively, the proportions of eyes that achieved UCVA of 20/40 or better (≥97%) exceeded the target rate (≥85%) across all postoperative study visits. The majority (≥51%) of eyes achieved 20/16 or better UCVA across all postoperative study visits. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 32 {32} **All Eyes (N=149)** | Acuity | Preoperative (n=149) | | 1 Month (n=146) | | 3 Months (n=149) | | 6 Months (n=96) | | 9 Months (n=89) | | 12 Months (n=88) | | 24 Months (n=69) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | 20/10 or better | 0 | 0.0% | 0 | 0.0% | 3 | 2.0% | 3 | 3.1% | 3 | 3.4% | 2 | 2.3% | 2 | 2.9% | | 20/12.5 or better | 0 | 0.0% | 16 | 11.0% | 19 | 12.8% | 14 | 14.6% | 19 | 21.3% | 11 | 12.5% | 7 | 10.1% | | 20/16 or better | 0 | 0.0% | 74 | 50.7% | 85 | 57.0% | 61 | 63.5% | 55 | 61.8% | 55 | 62.5% | 45 | 65.2% | | 20/20 or better | 0 | 0.0% | 134 | 91.8% | 137 | 91.9% | 88 | 91.7% | 82 | 92.1% | 81 | 92.0% | 60 | 87.0% | | 20/25 or better | 0 | 0.0% | 143 | 97.9% | 146 | 98.0% | 90 | 93.8% | 86 | 96.6% | 86 | 97.7% | 65 | 94.2% | | 20/32 or better | 4 | 2.7% | 145 | 99.3% | 149 | 100% | 95 | 99.0% | 88 | 98.9% | 86 | 97.7% | 66 | 95.7% | | 20/40 or better | 20 | 13.4% | 145 | 99.3% | 149 | 100% | 96 | 100% | 89 | 100% | 88 | 100% | 67 | 97.1% | | 20/50 or better | 57 | 38.3% | 146 | 100% | 149 | 100% | 96 | 100% | 89 | 100% | 88 | 100% | 68 | 98.6% | | 20/63 or better | 91 | 61.1% | 146 | 100% | 149 | 100% | 96 | 100% | 89 | 100% | 88 | 100% | 69 | 100% | | 20/80 or better | 107 | 71.8% | 146 | 100% | 149 | 100% | 96 | 100% | 89 | 100% | 88 | 100% | 69 | 100% | | 20/100 or better | 130 | 87.2% | 146 | 100% | 149 | 100% | 96 | 100% | 89 | 100% | 88 | 100% | 69 | 100% | | Worse than 20/100 | 19 | 12.8% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | $^{a}$ Preoperatively, 0.0% (0/149) of eyes achieved UCVA of 20/20 $^{b}$ Preoperatively, 13.4% (20/149) of eyes achieved UCVA of 20/40 Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per time period **Table 20** presents the differences in postoperative UCVA achieved compared to preoperative best spectacle corrected visual acuity (BSCVA) for all eyes. At 3 months, 83.9% (125/149) of eyes achieved the same or better acuity level postoperatively without correction as preoperatively with correction. PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 33 {33} **Postoperative UCVA Compared to Preoperative BSCVA All Eyes (N=149)** | Acuity | 1 Month (n=146) | | 3 Months (n=149) | | 6 Months (n=96) | | 9 Months (n=89) | | 12 Months (n=88) | | 24 Months (n=69) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | % | n | % | n | % | n | % | n | % | n | % | | > 2 lines better | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | 2 lines better | 2 | 1.4% | 6 | 4.0% | 8 | 8.3% | 10 | 11.2% | 3 | 3.4% | 2 | 2.9% | | 1 line better | 38 | 26.0% | 46 | 30.9% | 27 | 28.1% | 30 | 33.7% | 34 | 38.6% | 22 | 31.9% | | No change | 86 | 58.9% | 73 | 49.0% | 43 | 44.8% | 31 | 34.8% | 33 | 37.5% | 29 | 42.0% | | 1 lines worse | 14 | 9.6% | 20 | 13.4% | 12 | 12.5% | 14 | 15.7% | 15 | 17.0% | 11 | 15.9% | | 2 lines worse | 5 | 3.4% | 4 | 2.7% | 5 | 5.2% | 1 | 1.1% | 1 | 1.1% | 2 | 2.9% | | > 2 lines worse | 1 | 0.7% | 0 | 0.0% | 1 | 1.0% | 3 | 3.4% | 2 | 2.3% | 3 | 4.3% | | Not Reported | 0 | | 0 | | 0 | | 0 | | 0 | | 0 | | Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per time period PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 34 {34} c) 95% of eyes achieve refractive stability: Refractive stability was achieved at the 3 month study visit based on analyses performed using both a consecutive cohort (eyes with data at for at least two (2) consecutive study visits) and a consistent cohort (eyes with data at all periodic study exams through the stability point and at the confirmatory point). Results were similar between the two (2) cohorts and the criteria for determining refractive stability for both MRSE and MRC were met at 3 months, and confirmed at 6 months, in both cohorts. As shown in Tables 21-22, at least 95% of eyes had ≤1.00 D of change in MRSE (≥97.3%) and MRC (98.6%) between any two (2) visits, meeting the criterion of ≥95% of eyes with ≤1.00 D of change in MRSE and MRC. The mean rate of change was ≤0.007 D/month for MRSE and MRC between consecutive visits, meeting the criterion of ≤0.04 D/month. Also, the 95% confidence intervals of the mean rates of change in MRSE and MRC between consecutive exams included zero or a rate of change attributable to normal aging. TABLE 21 Stability of Manifest Refraction Spherical Equivalent (MRSE) Consecutive Cohortᵃ | Distributions | Between 1 & 3 Months (n=146) n % | Between 3 & 6 Months (n=96) n % | Between 6 & 9 Months (n=89) n % | Between 9 & 12 Months (n=87) n % | Between 12 & 24 Months (n=69) n % | | --- | --- | --- | --- | --- | --- | | Change in MRSE by <=0.50 D | 133 91.1% | 87 90.6% | 82 92.1% | 86 98.9% | 65 94.2% | | Change in MRSE by <=1.00 D | 142 97.3% | 96 100% | 89 100% | 86 98.9% | 68 98.6% | | Mean Outcomes | D +/-SD | D +/-SD | D +/-SD | D +/-SD | D +/-SD | | Mean Change in MRSE | 0.007 +/- 0.347 | -0.058 +/- 0.327 | 0.063 +/- 0.260 | -0.046 +/- 0.244 | -0.022 +/- 0.298 | | Mean Change Per Month | 0.003 | -0.019 | 0.021 | -0.015 | -0.002 | | Change defined as current visit value minus previous visit value | | | | | | | Confidence Intervals calculated based on Clopper-Pearson Exact method | | | | | | | ᵃ Includes only eyes with data at two consecutive visits | | | | | | PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 35 {35} **TABLE 22** **Stability of Absolute (Non-vector) Cylinder Consecutive Cohort**$^{a}$ | Magnitude of Change in Non-vector Cylinder Distributions | Between 1 & 3 Months (n=146) n % | Between 3 & 6 Months (n=96) n % | Between 6 & 9 Months (n=89) n % | Between 9 & 12 Months (n=87) n % | Between 12 & 24 Months (n=69) n % | | --- | --- | --- | --- | --- | --- | | Eyes with <=0.50 D Change | 142 97.3% | 92 95.8% | 88 98.9% | 85 97.7% | 67 97.1% | | Eyes with <=1.00 D Change | 146 100% | 96 100% | 89 100% | 87 100% | 68 98.6% | | **Mean Outcomes (D)** | | | | | | | Mean Change between Visit | -0.014 | 0.003 | 0.042 | 0.052 | -0.022 | | SD | 0.252 | 0.289 | 0.259 | 0.253 | 0.308 | | Mean Change Per Year | -0.082 | 0.01 | 0.169 | 0.207 | -0.022 | | Mean Change Per Month | -0.007 | 0.001 | 0.014 | 0.017 | -0.002 | | Change defined as current visit value minus previous visit value | | | | | | | Confidence Intervals calculated based on Clopper-Pearson Exact method | | | | | | | ^{a} Includes only eyes with data at two consecutive visits | | | | | | Mean manifest refractive outcomes over time are presented in **Table 23**. At 3 months, mean MRSE was -0.13 D (SD 0.39 D). **TABLE 23** **Mean Refractive Outcomes Over Time** **All Eyes (N=149)** | Variable | Preoperative n=149 | 1 Month n=146 | 3 Months n=149 | 6 Months n=96 | 9 Months n=89 | 12 Months n=88 | 24 Months n=69 | | --- | --- | --- | --- | --- | --- | --- | --- | | MRSE (D) +/-SD | -0.58 +/- 0.84 | -0.14 +/- 0.38 | -0.13 +/- 0.39 | -0.16 +/- 0.39 | -0.08 +/- 0.40 | -0.13 +/- 0.42 | -0.17 +/- 0.47 | | MRS (D) +/-SD | -2.07 +/- 1.05 | -0.29+/- 0.39 | -0.27+/- 0.40 | -0.34+/- 0.39 | -0.27+/- 0.36 | -0.34+/- 0.39 | -0.36+/- 0.46 | | MRC (D) +/-SD | 2.99 +/- 1.16 | 0.30+/- 0.30 | 0.29+/- 0.29 | 0.34+/- 0.30 | 0.38+/- 0.33 | 0.42+/- 0.33 | 0.38+/- 0.32 | MRSE = manifest refraction spherical equivalent MRS = manifest refractive sphere MRC = manifest refractive cylinder PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 36 {36} Table 24 presents the proportions of eyes with residual manifest cylinder magnitude at 3 months and the absolute shift in axis from preoperative. At 3 months, an axis shift of >30° from preoperative was noted for 26.8% (40/149) of eyes, and ten (25%; 10/40) of these eyes had a residual cylinder magnitude >0.50 D to 1.00 D. Nine (9) of these eyes achieved a UCVA of 20/25 or better; one (1) eye achieved a UCVA of 20/32. TABLE 24 Residual Astigmatic Axis Error (Non-Vector) at 3 Months All Eyes (N=149) | Residual Manifest Cylinder Magnitude | Absolute Shift in Axis | Total (N=149) | | --- | --- | --- | | -- Change^{a} (n=56) | 0° (n=5) | >0 to ≤ 5° (n=11) | >5 to ≤ 10° (n=10) | >10 to ≤ 15° (n=9) | >15 to ≤ 30° (n=18) | >30° (n=40) | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | 0.00 D | 56 | 100% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 56 | 37.6% | | >0.00 to ≤ 0.50 D | 0 | 0.0% | 1 | 20.0% | 9 | 81.8% | 8 | 80.0% | 7 | 77.8% | 18 | 100% | 30 | 75.0% | | 0.00 to ≤ 1.00 D | 0 | 0.0% | 4 | 80.0% | 2 | 18.2% | 2 | 20.0% | 2 | 22.2% | 0 | 0.0% | 10 | 25.0% | | Total | 56 | 100 | 5 | 100 | 11 | 100 | 10 | 100 | 9 | 100 | 18 | 100 | 40 | 100 | Percentage is calculated based on non-missing values. a No change in axis was calculated due to zero diopters (0.00 D) of manifest refractive cylinder at 3 months. Note: % Percentage is calculated by dividing the number of eyes in the cell / by the total number of eyes per column Vector analysis summary statistics at 3 months are presented in Table 25. At 3 months, the mean absolute error vector (EV) magnitude was less than 0.50 D (0.29 D; SD 0.29 D), the mean correction ratio (CR; ratio of surgically induced refractive change to intended refractive change) was close to 1.0 (0.98; SD 0.11) and the mean error ratio (ER) was close to zero (0.10; SD 0.10). PMA P930016/S045: FDA Summary of Safety and Effectiveness Data Page 37 {37} **Vector Analysis Summary at 3 Months** | Preoperative Cylinder Magnitude | n | |IRC| (Mean+/-SD) | |SIRC| (Mean+/-SD) | |EV| (Mean+/-SD) | CR (Mean+/-SD) | ER (Mean+/-SD) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | All | 149 | 2.99 +/- 1.16 | 2.90 +/- 1.10 | 0.29 +/- 0.29 | 0.98 +/- 0.11 | 0.10 +/- 0.10 | | ≥ 1.00 D to ≤ 2.00 D | 34 | 1.65 +/- 0.32 | 1.62 +/- 0.38 | 0.17 +/- 0.19 | 0.98 +/- 0.12 | 0.10 +/- 0.12 | | >2.00 D to ≤ 3.00 D | 59 | 2.57 +/- 0.25 | 2.58 +/- 0.41 | 0.31 +/- 0.29 | 1.00 +/- 0.13 | 0.12 +/- 0.12 | | >3.00 D to ≤ 4.00 D | 28 | 3.56 +/- 0.26 | 3.42 +/- 0.40 | 0.28 +/- 0.30 | 0.96 +/- 0.10 | 0.08 +/- 0.08 | | >4.00 D to ≤ 5.00 D | 18 | 4.56 +/- 0.27 | 4.29 +/- 0.43 | 0.43 +/- 0.29 | 0.94 +/- 0.07 | 0.10 +/- 0.07 | | >5.00 D to ≤ 6.00 D | 10 | 5.53 +/- 0.25 | 5.18 +/- 0.43 | 0.38 +/- 0.36 | 0.94 +/- 0.06 | 0.07 +/- 0.07 | IRC = Intended refractive change SIRC = Surgically induced refractive change EV = Error vector (IRC-SIRC) CR = Correction ratio (SIRC/IRC) ER = Error ratio (EV/IRC) ### 3. Factors Associated with Outcomes Covariate analyses of the preoperative variables found to have a difference among sites (contact lens wear, preoperative IDSE and preoperative IDS) and the factors found to be associated with primary effectiveness outcomes (preoperative IDS and IDC, and site) were performed. The results showed that none of the interactions with site were statistically significant. Additionally, demographic and preoperative variables were not found to have statistically significant effects on outcomes and there were no differences in outcomes due to the modified inclusion criterion. Thus, all data from all sites are poolable. Covariate analyses of significant factors showed that preoperative *iDesign Advanced WaveScan Studio* system refractive cylinder (IDC) had an effect on the accuracy of postoperative MRSE within 1.00 D. However, all outcomes stratification results met or exceeded study targets based on the factors evaluated. ### 4. Device Failures and Replacements There were no laser failures or replacements during the course of this study. There were six (6) *iDesign Advanced W…