STAR S4 IR Excimer Laser System and iDESIGN Refractive Studio

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION | Device Generic Name: | Ophthalmic Excimer Laser System Ophthalmic Refractometer | | --- | --- | | Device Trade Name: | *iDESIGN*® Refractive Studio and *STAR S4 IR*® Excimer Laser Systems | | Device Procode: | LZS | | Applicant’s Name and Address: | AMO Manufacturing USA, LLC 510 Cottonwood Dr Milpitas, CA 95035 | | Date of Panel Recommendation: | None | | Premarket Approval (PMA) | | | Application Number: | P930016/S057 | | Date of FDA Notice of Approval: | September 9, 2019 | The original *iDESIGN*® *Advanced WaveScan Studio* System was approved with the *STAR S4 IR*® Excimer Laser System for wavefront-guided laser assisted in situ keratomileusis (LASIK) for the correction of myopic refractive errors on May 6, 2015 in P930016/S044, for the correction of mixed astigmatic refractive errors on November 14, 2016 in P930016/S045, for the correction of hyperopic refractive errors on June 30, 2017 in P930016/S048, and for wavefront-guided monovision LASIK with *iDESIGN*® Refractive Studio System in myopic patients with presbyopia on June 15, 2018 in P930016/S053. This supplement expands the indication for use to include wavefront-guided photorefractive keratectomy (PRK). This supplement also includes a new updated software (v 2.1) for the *iDESIGN*® Refractive Studio system. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 1 {1} ## II. INDICATIONS FOR USE The STAR S4 IR® Excimer Laser System and the iDESIGN® Refractive Studio is indicated for wavefront-guided photorefractive keratectomy (PRK) in patients: - With myopia, with or without astigmatism, as measured by iDESIGN® Refractive Studio System with spherical equivalent up to -8.00 D, and cylinder up to -3.00 D. - With agreement between manifest refraction (adjusted for optical infinity) and iDESIGN® Refractive 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. - in patients 18 years of age or older, - with refractive stability (a change of ≤ 1.0 D in manifest refraction spherical equivalent for a minimum of 12 months prior to surgery) and - with wavefront capture diameter of at least 4 mm. ### III. CONTRAINDICATIONS iDESIGN® System driven PRK surgery is contraindicated: - in patients with any type of active connective tissue disease or autoimmune disease. - in patients with signs of keratoconus, abnormal corneal topography, and degenerations of the structure of the cornea. - in patients with significant dry eyes. If the patients have severely dry eyes, PRK 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 PRK. - in patients whose corneal thickness would cause anticipated treatment to violate the posterior 250 microns (μm) of the corneal stroma. - in patients with uncontrolled diabetes. - in patients with active eye infection or active inflammation - in patients with recent herpes eye infection or problems resulting from past infection PMA P930016/S057: 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® Refractive Studio system labeling. # V. DEVICE DESCRIPTION # A. iDESIGN® Refractive Studio The iDESIGN® Refractive Studio 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 the regular (sphero-cylindrical) refractive errors and irregularities (aberrations) that may cause decreased or blurry vision in the human eye. The iDESIGN® Refractive Studio system optical head projects a beam of light onto the retina. The light reflects through the optical path of the eye and into the Hartmann-Shack 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® Refractive Studio system software uses these data to compute refractive errors of the eye and wavefront aberrations using Fourier Transform analysis. The target treatment shape is automatically calculated by the iDESIGN® 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. # 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, 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 record the patient treatment. The variable spot scanning (VSS) feature of the laser, used for iDESIGN® procedure 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® systems utilize an automated iris registration system. The angle of rotation of the patient's eye under the PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 3 {3} 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® system camera. # VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the correction of myopia: - Glasses or contact lenses. - Implantable lens surgery (phakic intraocular lens). - Wavefront-guided or corneal topography-assisted LASIK. - LASIK, refractive lenticule extraction, or PRK using manifest refraction. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. # VII. MARKETING HISTORY The iDESIGN® Refractive Studio has been distributed in United States, Canada, Japan, India, Italy, Ireland, Great Britain, and Turkey. The STAR S4 IR® Excimer Laser and iDESIGN® Refractive Studio systems have been distributed in over 60 countries including Argentina, Australia, Austria, Bangladesh, Belgium, Bolivia, Brazil, Bulgaria, Cameroon, Canada, Chile, China, Colombia, Costa Rica, Cyprus, Czech Republic, Denmark, Ecuador, Egypt, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Iraq, Indonesia, Iraq, Ireland, Israel, Italy, Jamaica, Japan, Jordan, Kazakhstan, Korea, Kuwait, Lebanon, Malaysia, Martinique, Mexico, Mongolia, Netherlands, New Zealand, Norway, Oman, Paraguay, Peru, Philippines, Poland, Russian Federation, Saudi Arabia, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Tunisia, Turkey, United Arab Emirates, United Kingdom, United States, Venezuela, and Vietnam. Neither of these devices have been withdrawn from any country or market for reasons of safety or effectiveness. # VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (i.e., complications) associated with the use of the device: decrease in best corrected visual acuity (vision that is corrected with glasses or contact lenses), over-correction or under-correction that may require eyeglasses or contact lens wear, increase in astigmatism, a reduction in the refractive correction over time (regression), unintentional imbalance between the two eyes (anisometropia) that may cause headaches, eye strain, double vision and/or difficulty judging distance or depth perception, patients around 40 years of age or older may need glasses for close work such as reading due to presbyopia, foreign body sensations, pain (including chronic eye pain that is resistant to therapy referred to as neuropathic pain), dry eyes, halos, glare, starbursts, hazy PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 4 {4} vision, blurred vision, distortion, double or multiple images (ghost images, images that appear to have a shadow), fluctuating vision, difficulty focusing, difficulty with night driving, eye pain or soreness, feeling of something in the eye, grittiness, light sensitivity, decreased ability to see in low-light conditions (e.g., reading a street sign at dusk), corneal damage (scarring, swelling, cloudiness, haziness, irregular shape, bulging of the cornea (ectasia)), corneal epithelial defect, corneal erosion, corneal ulceration or perforation, corneal decompensation, persistent corneal edema, corneal infection and corneal inflammation, drooping eyelid (ptosis) that may require surgical intervention, increased intraocular pressure, cataract, and retinal detachment. Also, there may be difficulty with for future ophthalmic assessments, such as appropriate intraocular lens selection for implantation during cataract surgery and intraocular pressure (IOP) assessments. For the specific adverse events that occurred in the pivotal clinical trial, please see **Section X** (Summary of Primary Clinical Study) below. ## IX. SUMMARY OF NONCLINICAL STUDIES ### *iDESIGN®* Refractive Studio Non-clinical testing was performed to verify and validate the version 2.1 software incorporated into *iDESIGN®* Refractive Studio to ensure the system meets its design requirements. Supplemental Use Case Testing was conducted for the user interface changes of the PRK indication, and the slow Autorefraction option. ### *STAR S4 IR®* Excimer Laser System Since there were no changes to the hardware in this supplement, the hardware verification testing performed and submitted previously is still applicable. For a summary of the nonclinical studies, please refer to the SSED of the original PMA P930016 (https://www.accessdata.fda.gov/cdrh_docs/pdf/p930016.pdf) and P930016/S44 (https://www.accessdata.fda.gov/cdrh_docs/pdf/P930016S044b.pdf). ## X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of wavefront-guided photorefractive keratectomy (PRK) using the *iDESIGN®* Refractive Studio and *STAR S4 IR®* Excimer Laser System for patients with myopia, with or without astigmatism, as measured by *iDESIGN®* Refractive Studio with spherical equivalent up to -10.00 D, and cylinder up to -4.00 D in the US under IDE G150113. A summary of the clinical study is presented below. ### A. Study Design PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 5 {5} Patients were treated between February 2016 and August 2017. The database for this Panel Track Supplement reflected data collected through November 24, 2017* and included 167 subjects. There were 7 investigational sites. The study was a single-arm, 1-year, prospective, multicenter, bilaterally-treated, open-label, non-randomized clinical study. As refractive stability was reached at 6 months (and confirmed at 9 months), the key safety and effectiveness endpoints are evaluated at 6 months. At the time of database closure for this analysis, 322 eyes (96.4%; 322/334) were evaluated at 6 months, 228 eyes (68.3%; 228/334) were evaluated at 9 months, and 184 eyes (55.1%; 184/334) were evaluated at 12 months. Descriptive statistics (including sample size [n], mean, standard deviation [SD], minimum, maximum, as appropriate) and frequency distributions were used to summarize clinical outcomes. Confidence intervals for binomial proportions were computed using the Clopper-Pearson exact method. All confidence intervals, statistical tests, and resulting p-values were based on two-sided analyses and assessed at a 0.05 significance level. For continuous variables, statistical tests assuming normality were generally used. However, the data were reviewed to evaluate whether the normality assumption was appropriate. When found not to be appropriate, the corresponding non-parametric tests were used. For visual acuity data, Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores were converted to LogMAR values prior to analysis. For refractive data, 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 equivalent (MRSE) was calculated using the adjusted manifest sphere value. Additionally, all refractions were converted to minus cylinder format and adjusted for vertex distance (standardized to 12.5 mm). Outcomes stratifications of the key effectiveness and safety endpoints were conducted by age, gender, race, site, preoperative contact lens wear, preoperative iDesign spherical equivalent (IDSE), preoperative iDesign sphere (IDS), preoperative iDesign cylinder (IDC), wavefront capture diameter, iris registration status, and clinically significant protocol deviations. Additionally, covariate analyses of the effect on key study endpoints for any factors found to have statistically significant differences among stratification categories were conducted. Per ANSI Z80.11-2012, Annex E, the sample size calculation is to be based on the probability of observing an adverse event at a rate greater than or equal to the expected rate but less than or equal to an acceptable target. This study was powered to detect the percentage of eyes losing 2 or more lines of BSCVA at 3 months. In the approved indication for the original *STAR S4 IR®* System wavefront-guided LASIK Myopia clinical study (PMA P930016-S016, approved 05/23/03), the percentage of eyes losing 2 or more lines of BSCVA at 3 months was 0.3% (1/318, 95% exact CI (0.00%, 1.7%)). Using the binomial distribution with an alpha of 0.05, 80% power and a sample size of n=300 eyes, a rate of at least 1% can be detected. Adding 15% for loss due to attrition yields a sample size of 334 eyes (167 subjects) to be treated in order to achieve 300 evaluable eyes at the * The vector analysis included on Table 33 was based on 324 evaluable patients at the 6-month time-point at final database lock on August 24, 2018. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 6 {6} point of refractive stability. Adding an additional 50% to account for screen failures allowed approximately 334 subjects to be enrolled. Sample size was also calculated for the contrast sensitivity substudy. The sample size calculation for the substudy was based on ANSI guidance (ANSI Z80.11) using non-inferiority approach. With a sample size of 65, a paired t-test with a 0.05 one-sided significance level would have over 90% power to detect the paired difference in mean contrast sensitivity was no less than 0.15 below zero when the expected mean difference was 0, assuming the non-inferiority margin equals 0.15 and the standard deviation of the differences was 0.40. ### 1. Subject Selection and Eligibility Criteria Enrollment in this study was limited to subjects who met the following eligibility 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 both eyes and intend to have bilateral PRK for the treatment of myopic refractive errors. In general, eyes were to be healthy with myopic refractive errors of up to -10.00 D of spherical equivalent with cylinder between 0.00 and -4.00 D, as measured using the iDESIGN® aberrometer. #### 1. Clinical Inclusion and Exclusion Criteria Enrollment in this study was limited to patients who met the following inclusion criteria. ##### i. Subject Inclusion Criteria - Signed informed consent and HIPAA authorization. - At least 18 years of age. - The refractive error, based on the iDESIGN® displayed refraction selected for treatment (“4.0 Rx calc” at 12.5 mm), must be myopia with or without astigmatism with sphere up to -8.00 D, and cylinder between 0.00 D and -4.00 D with a maximum spherical equivalent (SE) of -10.00 D. - Anticipated residual stromal bed thickness of at least 250 microns. - Distance best spectacle corrected visual acuity (BSCVA) of 20/20 or better. - BSCVA ≥ 2 lines (≥ 10 letters) better than distance uncorrected visual acuity (UCVA). - 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 MRSE. - Demonstration of refractive stability for subjects with contact lens wear within the last 4 weeks: rigid contact lenses must be removed for at least 4 weeks and soft contact lenses for at least 2 weeks prior to the first refraction used to establish stability. - Agreement between manifest refraction (adjusted for optical infinity) and iDESIGN® System refraction chosen for treatment PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 7 {7} Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: - • Women who are pregnant, breast-feeding, or intend to become pregnant, or not using an adequate method of birth control over the course of the study. - • 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, severe dry eye syndrome or symptoms, neovascularization > 1 mm from limbus), retinal detachment/repair, clinically significant lens opacity, clinical evidence of trauma, corneal opacity within the central 9 mm and visible on topography, at risk for developing strabismus, or with ocular hypertension, intraocular pressure (IOP) >21 mmHg at screening or evidence of glaucoma or propensity for narrow angle glaucoma. - • Evidence of keratoconus, corneal dystrophy or irregularity, or abnormal topography. - • Desire to have monovision. ## 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations as follows: ### Clinical Study Visit Schedule | VISIT | EXAM | VISIT WINDOW | | --- | --- | --- | | 1 | Preoperative Exam | Within 120 days prior to surgery | | 2 | Operative | 0-120 days after preoperative exam | | 3 | 1 day | 1-2 day postoperative | | 4 | 1 week | 5-8 days postoperative | | 5 | 1 month | 3-6 weeks postoperative | | 6 | 3 months | 10-14 weeks postoperative | | 7 | 6 months | 20-26 weeks postoperative | | 8 | 9 months | 35-43 weeks postoperative | | 9 | 12 months | 44-60 Weeks postoperative | | Note: 1 month = 4 weeks, 1 week = 7 days | | | Study procedures included uncorrected distance visual acuity (monocular and binocular), best spectacle corrected distance visual acuity (monocular), contrast sensitivity, manifest PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 8 {8} refraction, cycloplegic refraction, anterior segment examination, Schirmer I tear test, IOP, corneal pachymetry, keratometry, corneal topography, dilated fundus examination, non-directed ocular/visual symptoms query iDESIGN® System measurements (refraction, aberrometry, topography, keratometry, and pupillometry), and binocular subjective questionnaires. Adverse events and complications were recorded at all visits. In this study, all eyes were targeted for emmetropia. Surface PRK treatments were calculated using iDESIGN® software version 1.3. Preoperatively, study procedures included: - Subjective non-directed ocular/visual symptoms - Binocular Subjective Questionnaires: Ocular Surface Disease Index (OSDI), Patient Reported Visual Symptom Questionnaire (PRVSQ for PRK/LASIK), National Eye Institute Refractive Error Quality of Life - 42 (NEI-RQL-42) and exploratory Satisfaction Questionnaire - iDESIGN® System Measurement (refraction, aberrometry, topography, keratometry, pupillometry) - Keratometry - Corneal topography - Distance UCVA – (monocular and binocular) - Manifest refraction - Distance BSCVA - Contrast sensitivity substudy - Anterior segment examination - Schirmer I Tear Test - Intraocular pressure (applanation tonometry) - Pachymetry (ultrasound) - Cycloplegic refraction - Dilated fundus examination Postoperatively, the parameters measured during the study included: - Non-directed ocular/visual symptoms - Binocular Subjective Questionnaires: OSDI, PRVSQ for PRK/LASIK, NEI RQL 42 and exploratory Satisfaction Questionnaire - iDESIGN® System Measurement (refraction, aberrometry, topography, keratometry, pupillometry) - Keratometry - Corneal topography - Distance UCVA – (monocular and binocular) - Manifest refraction - BSCVA; (if ≥ 2-line loss in BSCVA at 3 months or later, a rigid contact lens over refraction or pin-hole visual acuity should be obtained) - Anterior segment examination - Contrast sensitivity substudy - Schirmer I Tear Test PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 9 {9} - Intraocular pressure (applanation tonometry) - Pachymetry (ultrasound) (1 and 12-months only) - Cycloplegic refraction (6 and 12-months only) - Dilated fundus examination (6 and 12-months only) - AEs, complications, and device deficiencies/complaints were recorded at all visits. The key timepoints are shown below in the tables summarizing safety and effectiveness. ### 3. Clinical Endpoints With regard to safety: #### Primary Safety Endpoint Targets 1. Maintenance of BSCVA-lines lost - <5% of eyes with a loss of >2 lines of BSCVA from preoperative - <1% of eyes with haze beyond 6 months with loss >2 lines of BSCVA 2. Maintenance of BSCVA-preservation 20/40 - <1% of eyes with a BSCVA of 20/20 or better preoperatively had BSCVA of worse than 20/40 postoperatively 3. Induced manifest refractive astigmatism - <5% of eyes with induced manifest refractive astigmatism >2.00 D 4. Serious, device-related adverse events - <1% of eyes with serious, device-related adverse events per type of event With regard to effectiveness: #### Primary Effectiveness Endpoint Targets 1. Monocular UCVA - ≥ 85% of eyes with a UCVA of 20/40 or better 2. MRSE within 0.50 D of target - ≥ 50% of eyes with an MRSE within 0.50 D of intended correction 3. MRSE within 1.00 D of target - ≥ 75% of eyes with an MRSE within 1.00 D of intended correction 4. Refractive stability - ≥ 95% of eyes achieve refractive stability. The targets were to be evaluated at the point of postoperative refractive stability. The point of refractive stability in the study was determined when the following criteria were met: •At least 95% of the treated eyes have a change ≤1.00 D of MRSE and manifest cylinder (MRC) between refractions performed at 1 month and 3 months after surgery or any two refractions performed at least 3 months apart. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 10 {10} •The mean rate of change in MRSE and MRC, as determined by a paired analysis, is ≤0.5 D per year (0.04 D/month) over the same time period. •The mean rate of change in MRSE and MRC decreases monotonically over time, with a projected asymptote of zero or a rate of change attributable to normal aging. •The 95% confidence interval for the mean rate of change includes zero or a rate of change attributable to normal aging. •Stability is confirmed at least 3 months after the stability time point by a statistically adequate subgroup. # **B. Accountability of PMA Cohort** At the time of database lock, of the 334 eyes enrolled in the PMA study, 96.4% (322) of eyes are available for analysis at the 6-month post-operative visit, the point of postoperative refractive stability. **Table 1** presents the accountability for the 334 eyes treated in this study. All 167 subjects were treated bilaterally. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 11 {11} **TABLE 1** Accountability | Accountability All Treated Eyes (N=334) Subject status | 1 Day | | 1 Week | | 1 Month | | 3 Month | | 6 Month | | 9 Month | | 12 Month | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | **Available for Analysis** | 334 | 100.0 | 334 | 100.0 | 332 | 99.4 | 328 | 98.2 | 322 | 96.4 | 228 | 68.3 | 184 | 55.1 | | - In Interval (included in analysis) | 334 | 100.0 | 332 | 99.4 | 330 | 98.8 | 310 | 92.8 | 300 | 89.8 | 222 | 66.5 | 180 | 53.9 | | - Out of Interval (included in analysis) | 0 | 0.0 | 2 | 0.6 | 2 | 0.6 | 18 | 5.4 | 22 | 6.6 | 6 | 1.8 | 4 | 1.2 | | **Missing Eyes** | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | 6 | 1.8 | 10 | 3.0 | 20 | 6.0 | 22 | 6.6 | | - Discontinued | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | - Missed visit | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 4 | 1.2 | 2 | 0.6 | 2 | 0.6 | 0 | 0.0 | | - Not seen but accounted for | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | - Lost-to-follow-up | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | 2 | 0.6 | 8 | 2.4 | 18 | 5.4 | 22 | 6.6 | | **Active** | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | 86 | 25.7 | 128 | 38.3 | | - Active (not yet in visit interval) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | 58 | 17.4 | 104 | 31.1 | | - In interval or Past interval (form not yet received) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 28 | 8.4 | 24 | 7.2 | | Percent Accountability* (ANSI Z80.11-2012) | . | 100.0 | . | 100.0 | . | 99.4 | . | 98.2 | . | 97.0 | . | 91.9 | . | 89.3 | *Percent Accountability = (Available for Analyses * 100)/(Enrolled [treated] - Discontinued - Active) PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 12 {12} ### C. Study Population Demographics and Baseline Parameters The demographics and eligibility criteria of the study population are typical for a contemporary refractive study performed in the US with the exception of gender/sex. Although females are not equally represented in the study, the outcomes from the study are transferable to the typical refractive surgical population because females are adequately represented in the study. Subgroup analyses (**Section X, D.3**) show that all key safety and effectiveness targets were met when stratified by age, sex/gender, and race. Subject demographics are presented in **Table 2**. The mean age of the study subjects were 26.6 years (SD 5.41) and ranged from 19 to 47 years. The majority of subjects were White (65.9%; 110/167). The subject population consisted of more males (68.3%) than females (31.7%). The majority of subjects (97.0%; 162/167) did not wear contact lenses within the 4 weeks prior to the screening visit. **Demographic Characteristics** | Category | Classification | All Subjects (N=167) | | --- | --- | --- | | Gender | Male | 114 (68.3%) | | | Female | 53 (31.7%) | | Race | American Indian/Alaska Native | 3 (1.8%) | | | Asian (Includes Indian) | 12 (7.2%) | | | Black or African American | 22 (13.2%) | | | White | 110 (65.9%) | | | Other^{a} | 20 (12.0%) | | Age (Years) | Mean | 26.6^{b} | | | SD | 5.41 | | | Min | 19 | | | Max | 47 | | Preoperative CL Wear^{c} | No | 162 (97.0%) | | | Soft | 5 (3.0%) | | | Rigid/Toric | 0 (0.0%) | | | Soft/Toric | 0 (0.0%) | $^{a}$ Other includes Hispanic and Mixed. $^{b}$ There were 54 eyes from subjects 18-21 years old. $^{c}$ Within the 4 weeks (28 days) prior to the screening visit. **Table 3** presents the mean preoperative manifest and *iDESIGN®* System measured refractive error for the 334 treated eyes. Mean preoperative refractive measurements were consistent between *iDESIGN®* and manifest refractions with almost no difference in means (all within 0.05 D of each other). PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 13 {13} **Preoperative Manifest and *iDESIGN*® System Refractive Errors** | | Variable | Mean | Std Dev | Median | Minimum | Maximum | | --- | --- | --- | --- | --- | --- | --- | | **Manifest Refraction** | **MRS** | -3.58 | 1.96 | -3.25 | -8.25 | -0.25 | | | **MRC** | -1.00 | 0.84 | -0.75 | -4.00 | 0.00 | | | **MRSE** | -4.08 | 1.97 | -3.75 | -8.75 | -0.63 | | **iDesign Refraction** | **IDS** | -3.56 | 1.96 | -3.23 | -7.99 | -0.07 | | | **IDC** | -1.05 | 0.83 | -0.80 | -3.98 | -0.03 | | | **IDSE** | -4.09 | 1.97 | -3.69 | -8.99 | -0.64 | | MRS = manifest refractive sphere | | IDS = iDesign sphere | | | | | | MRC = manifest refractive cylinder | | IDC = iDesign cylinder | | | | | | MRSE = manifest refractive spherical equivalent | | IDSE = iDesign spherical equivalent | | | | | **Tables 4 and Table 5** present the preoperative refractive error bin distributions for the study population based on preoperative *iDESIGN*® System measurements. **Preoperative Refractive Error Stratified by *iDESIGN*® Sphere and Cylinder** | **iDesign Sphere** | **0 to ≥-0.5 D** | | **<-0.5 to ≥-1 D** | | **<-1 to ≥-2 D** | | **<-2 to ≥-3 D** | | **<-3 to ≥-4 D** | | **Total** | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | **n** | **%** | **n** | **%** | **n** | **%** | **n** | **%** | **n** | **%** | **n** | **%** | | ≤0 to ≥-1 D | 8 | 2.4% | 5 | 1.5% | 2 | 0.6% | 4 | 1.2% | 4 | 1.2% | 23 | 6.9% | | <-1 to ≥-2 D | 19 | 5.7% | 22 | 6.6% | 16 | 4.8% | 8 | 2.4% | 2 | 0.6% | 67 | 20.1% | | <-2 to ≥-3 D | 12 | 3.6% | 17 | 5.1% | 22 | 6.6% | 7 | 2.1% | 2 | 0.6% | 60 | 18.0% | | <-3 to ≥-4 D | 19 | 5.7% | 17 | 5.1% | 17 | 5.1% | 1 | 0.3% | 2 | 0.6% | 56 | 16.8% | | <-4 to ≥-5 D | 13 | 3.9% | 17 | 5.1% | 9 | 2.7% | 4 | 1.2% | 0 | 0.0% | 43 | 12.9% | | <-5 to ≥-6 D | 15 | 4.5% | 9 | 2.7% | 8 | 2.4% | 2 | 0.6% | 3 | 0.9% | 37 | 11.1% | | <-6 to ≥-7 D | 9 | 2.7% | 7 | 2.1% | 8 | 2.4% | 3 | 0.9% | 1 | 0.3% | 28 | 8.4% | | <-7 to ≥-8 D | 6 | 1.8% | 4 | 1.2% | 8 | 2.4% | 2 | 0.6% | 0 | 0.0% | 20 | 6.0% | | **Total** | **101** | **30.2%** | **98** | **29.3%** | **90** | **26.9%** | **31** | **9.3%** | **14** | **4.2%** | **334** | **100%** | % Percentage is calculated by dividing the total number of eyes in the bin (n)/ by the total number of eyes N (334) **Spherical Equivalent (SE) and Cylinder, All Treated Eyes (N=334)** | **iDesign SE** | **0 to ≥-0.5 D** | | **<-0.5 to ≥-1 D** | | **<-1 to ≥-2 D** | | **<-2 to ≥-3 D** | | **<-3 to ≥-4 D** | | **Total** | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | **n** | **%** | **n** | **%** | **n** | **%** | **n** | **%** | **n** | **%** | **n** | **%** | | ≤0 to ≥-1 D | 3 | 0.9% | 2 | 0.6% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 5 | 1.5% | | <-1 to ≥-2 D | 21 | 6.3% | 18 | 5.4% | 6 | 1.8% | 3 | 0.9% | 0 | 0.0% | 48 | 14.4% | | <-2 to ≥-3 D | 12 | 3.6% | 13 | 3.9% | 20 | 6.0% | 7 | 2.1% | 5 | 1.5% | 57 | 17.1% | | <-3 to ≥-4 D | 20 | 6.0% | 25 | 7.5% | 21 | 6.3% | 7 | 2.1% | 2 | 0.6% | 75 | 22.5% | | <-4 to ≥-5 D | 11 | 3.3% | 14 | 4.2% | 11 | 3.3% | 3 | 0.9% | 1 | 0.3% | 40 | 12.0% | | <-5 to ≥-6 D | 13 | 3.9% | 15 | 4.5% | 10 | 3.0% | 4 | 1.2% | 2 | 0.6% | 44 | 13.2% | | <-6 to ≥-7 D | 14 | 4.2% | 6 | 1.8% | 10 | 3.0% | 2 | 0.6% | 1 | 0.3% | 33 | 9.9% | | <-7 to ≥-8 D | 4 | 1.2% | 5 | 1.5% | 7 | 2.1% | 2 | 0.6% | 3 | 0.9% | 21 | 6.3% | | <-8 to ≥-9 D | 3 | 0.9% | 0 | 0.0% | 5 | 1.5% | 3 | 0.9% | 0 | 0.0% | 11 | 3.3% | | **Total** | **101** | **30.2%** | **98** | **29.3%** | **90** | **26.9%** | **31** | **9.3%** | **14** | **4.2%** | **334** | **100%** | % Percentage is calculated by dividing the number of eyes in the bin (n)/ by the total number of eyes N (334) PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 14 {14} ## D. Safety and Effectiveness Results As refractive stability was achieved at 6 months, and confirmed at 9 months, the key safety and effectiveness study endpoints were evaluated at 6 months for all treated eyes (N = 334). ### 1. Safety Results The analysis of safety was based on the safety cohort of 334 treated eyes with 322 available at 6 months. The key safety outcomes for this study are presented below in Tables 6 to 8. Adverse effects are reported in Table 9. a) Less than 5% of eyes with a loss of >2 lines BSCVA from preoperative: At 6 months, 1/322 eyes (0.3%) lost >2 lines of BSCVA, meeting the safety criterion of <5% of eyes with a loss of >2 lines of BSCVA. b) Less than 1% of eyes with haze beyond 6 months with a loss of >2 lines BSCVA from preoperative: One eye (0.3%, 1/322 eyes) had haze beyond 6 months and lost >2 lines of BSCVA, meeting the safety criterion of <1% of eyes with haze beyond 6 months with a loss of >2 lines BSCVA from preoperative. c) Less than 1% of eyes with a BSCVA of 20/20 or better preoperatively that have a BSCVA of worse than 20/40 postoperatively: No eyes (0%; 0/322) had preoperative BSCVA of 20/20 or better but worse than 20/40 postoperatively at 6 months, meeting the safety endpoint target of <1% of eyes with preoperative BSCVA of 20/20 or better having BSCVA worse than 20/40 postoperatively. d) Less than 5% of eyes with induced manifest refractive astigmatism >2.00 diopters: At 6 months, no eyes (0%; 0/322) had induced manifest refractive astigmatism >2.00 D, meeting the safety criterion of <5% of eyes with induced manifest refractive astigmatism >2.00 D. e) Less than 1% of eyes with serious, device-related AEs per type: Serious, devise-related AEs occurred ≤ 0.9% per type, meeting the target rate of <1% per type. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 15 {15} # **TABLE 6** **Summary of Study Safety Endpoints Over Time – All Eyes** | Safety Variable | 1 Month (N=332) | 3 Months (N=328) | 6 Months (N=322) | 9 Months (N=228) | 12 Months (N=184) | | --- | --- | --- | --- | --- | --- | | | n % | n % | n % | n % | n % | | Loss of > 2 lines BSCVA from preoperative^{a} | 3 0.9% | 0 0% | 1^{f} 0.3% | 0 0% | 0 0% | | Haze beyond 6 months with loss >2 lines of BSCVA^{b} | | | 1^{f} 0.3% | 0 0% | 0 0% | | BSCVA of 20/20 preoperative and 20/40 postoperative^{c} | 0 0% | 0 0% | 0 0% | 0 0% | 0 0% | | Induced manifest refractive astigmatism >2.00 D^{d} | 0 0% | 0 0% | 0 0% | 0 0% | 0 0% | | **Cumulative** | | | | | | | Serious, device-related adverse events^{e} | ≤ 0.9% of eyes with each type of serious, device-related adverse event (corneal infiltrate 0.6% [2/334], corneal erosion 0.6% [2/334], corneal haze (visually significant or potentially affecting vision) 0.9% [3/334]) | | | | | | Note: Shaded areas represent time frames outside event definition. | | | | | | | % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N) [= (n / N) x 100% ]. | | | | | | | ^{a} Safety endpoint target: <5% of eyes with a loss of >2 lines (logMAR change of >0.24) of BSCVA from preoperative | | | | | | | ^{b} Safety endpoint target: <1 % of eyes with haze beyond 6 months with loss >2 lines (logMAR change of >0.24) of BSCVA | | | | | | | ^{c} Safety endpoint target: <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 | | | | | | | ^{d} Safety endpoint target: <5% of eyes with induced manifest refractive astigmatism >2.00 D | | | | | | | ^{e} Safety endpoint target: <1% of eyes for each type of serious, device-related adverse events | | | | | | | ^{f} One eye had haze and a decrease in BSCVA of 2 lines from preoperative BSCVA of 20/16 to 20/25 at 6 months: BSCVA improved to 20/12.5 at 9 months. | | | | | | PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 16 {16} # f) *BSCVA Preservation* **Table 7** shows that 99.7% of eyes in the clinical study had 20/20 or better BSCVA at 6 months after treatment. **BSCVA Before and After Treatment – All Eyes** | Visual Acuity | Preoperative (N=334) | | 1 Month (N=332) | | 3 Months (N=328) | | 6 Months (N=322) | | 9 Months (N=228) | | 12 Months (N=184) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | | 20/10 or better | 12 | 3.6% | 13 | 3.9% | 72 | 22.0% | 82 | 25.5% | 58 | 25.4% | 55 | 29.9% | | 20/12.5 or better | 167 | 50.0% | 139 | 41.9% | 245 | 74.7% | 256 | 79.5% | 184 | 80.7% | 149 | 81.0% | | 20/16 or better | 315 | 94.3% | 271 | 81.6% | 322 | 98.2% | 319 | 99.1% | 228 | 100% | 182 | 98.9% | | 20/20 or better | 334 | 100% | 326 | 98.2% | 328 | 100% | 321 | 99.7% | 228 | 100% | 184 | 100% | | 20/25 or better | 334 | 100% | 331 | 99.7% | 328 | 100% | 322 | 100% | 228 | 100% | 184 | 100% | | 20/32 or better | 334 | 100% | 332 | 100% | 328 | 100% | 322 | 100% | 228 | 100% | 184 | 100% | | 20/40 or better | 334 | 100% | 332 | 100% | 328 | 100% | 322 | 100% | 228 | 100% | 184 | 100% | % Percentage is calculated by dividing the number of eyes in the cell (n) by the total number of eyes per time period (N). The change in lines of BSCVA postoperatively compared to preoperatively for all eyes is presented in **Table 8**. At 6 months, 97.2% (313/322) of eyes had either no change or an improvement in BSCVA compared to preoperative. One eye (0.3%; 1/322) had a decrease in BSCVA of >2 lines at 6 months vs. preoperative, meeting the safety endpoint target for BSCVA lines lost of <5% of eyes with a loss of >2 lines of BSCVA. **Change in BSCVA Over Time vs. Preoperative – All Eyes** | LogMAR Change | Acuity Change | 1 Month (N=332) | | 3 Months (N=328) | | 6 Months (N=322) | | 9 Months (N=228) | | 12 Months (N=184) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | n | % | n | % | n | % | n | % | n | % | | <-0.24 | Increase >2 lines | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | ≥-0.24 to <-0.14 | Increase =2 lines | 1 | 0.3% | 6 | 1.8% | 10 | 3.1% | 10 | 4.4% | 18 | 9.8% | | ≥-0.14 to <-0.04 | Increase =1 line | 40 | 12.0% | 134 | 40.9% | 151 | 46.9% | 124 | 54.4% | 108 | 58.7% | | ≥-0.04 to ≤0.04 | No Change | 196 | 59.0% | 174 | 53.0% | 152 | 47.2% | 90 | 39.5% | 56 | 30.4% | | >0.04 to ≤0.14 | Decrease =1 line | 77 | 23.2% | 13 | 4.0% | 8 | 2.5% | 4 | 1.8% | 2 | 1.1% | | >0.14 to ≤0.24 | Decrease =2 lines | 15 | 4.5% | 1 | 0.3% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | >0.24 | Decrease >2 lines | 3 | 0.9% | 0 | 0.0% | 1 | 0.3% | 0 | 0.0% | 0 | 0.0% | | Not Reported | | 0 | | 0 | | 0 | | 0 | | 0 | | | Total | | 332 | | 328 | | 322 | | 228 | | 184 | | % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N). One eye had a decrease in BSCVA from the 20/16 line preoperatively to the 20/25 line at 6 months postoperatively (Decrease > 2 lines). BSCVA improved to the 20/12.5 line at 9 months postoperatively. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 17 {17} g) Adverse effects that occurred in the PMA clinical study: A summary of serious and non-serious AEs is presented in Table 9. During the study, the most frequently reported AEs were corneal edema at 1 month (rate of 3%; 10/334); all resolved by 3 months. At the stability time point of 6 months, AEs included haze beyond 6 months with loss of 2 lines or greater (≥10 letters) BSCVA and decrease in BSCVA of greater than or equal to 2 lines (≥10 letters) not due to irregular astigmatism (both 0.3%, 1/322; same eye), corneal haze potentially affecting vision (0.6%, 2/322; both eyes of same subjects), corneal erosion (0.3%; 1/322), and anterior uveitis (0.3%; 1/322). A total of 11 serious ocular AEs occurred in 11 eyes of 10 subjects. - Four serious, non-device related AEs occurred in 4 eyes of 4 subjects: retinal detachment (n = 1), anterior uveitis (n = 1), and corneal abrasion (n = 2). - Seven serious, device-related AEs (SADEs) occurred in 7 eyes of 6 subjects: corneal infiltrate (n = 2 eyes), corneal haze (n = 3 eyes), and corneal erosion (n = 2 eyes). The rate of each type of serious, device-related adverse event was <1% (corneal infiltrate: 0.6%, 2/334; corneal erosion: 0.6%, 2/334; corneal haze: 0.9%, 3/334), meeting the safety endpoint for serious, device-related AEs. All seven SADEs have resolved. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 18 {18} **TABLE 9** **Summary of Adverse Events Over Time – All Eyes** | Adverse Event | <1 Month (N=334) | | 1 Month (N=332) | | 3 Months (N=328) | | 6 Months (N=322) | | 9 Months (N=228) | | 12 Months (N=184) | | Cumulative^{a} (N=334) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | Corneal infiltrate or ulcer | 2 | 0.6 | 0 | 0.0 | 1 | 0.3 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 3 | 0.9 | | Any persistent corneal epithelial defect at 1 month or later^{b} | | | 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^{c} | | | 10 | 3.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 10 | 3.0 | | 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 | | Haze beyond 6 months with loss of 2 lines or greater (≥10 letters) | | | | | | | 1^{d} | 0.3 | 0 | 0.0 | 0 | 0.0 | 1^{d} | 0.3 | | 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 | 1^{d} | 0.3 | 0 | 0.0 | 0 | 0.0 | 1^{d} | 0.3 | | Retinal detachment | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.5 | 1 | 0.3 | | Retinal vascular accidents | 0 | 0.0 | 0 | 0.0 | 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 | | 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 | | Corneal melt | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Glaucoma or ocular hypertension | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Severe allergic reaction to study medication | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Any other vision-threatening event (Serious) | | | | | | | | | | | | | | | | Corneal haze potentially affecting vision | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2^{e} | 0.6 | 0 | 0.0 | 0 | 0.0 | 2^{e} | 0.6 | | Corneal abrasion | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | | Corneal erosion | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.3 | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | | Anterior uveitis | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.3 | 0 | 0.0 | 0 | 0.0 | 1 | 0.3 | | Other adverse events (Non-serious) | | | | | | | | | | | | | | | | Corneal erosion | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.3 | | Chronic dry eye^{f} | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | | Headaches | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | Note: Shaded areas represent time frames outside event definition. % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N). $^{a}$ Cumulative includes unscheduled visits. $^{b}$ Defined as corneal epithelial defect as a result of surgery that persisted at 1 month or later. $^{c}$ Includes only cases involving primary cases of corneal edema (i.e., does not include cases of edema secondary to corneal infiltrate, corneal erosion, and corneal abrasion) $^{d}$ Same eye (#30352) $^{e}$ Both eyes from same subject (#2051) $^{f}$ Chronic Dry Eye diagnosis was not based on the protocol-defined dry eye definition (subject score of ≥ 33 on the OSDI in combination with a Schirmer score of ≤ 5 mm). PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 19 {19} # h) *Complications* **Table 10** presents a summary of complications (per the statistical plan and consistent with the ANSI Guidance Document for Corneal Reshaping, Z80.11-2012) over time. The highest frequencies of reports of complications occurred between 1 week and <1 month. Corneal edema was reported in 34.7% of eyes (116/334); most reports were Grade 1 (82.8%; 96/116). Ghosting/diplopia was reported by 44.3% of subjects (74/167; via a PRVSQ PRO questionnaire) prior to 1 month; rates decreased over time. During the study, other complications included pain (highest rate at 6 months: 3.4%, 11/322), foreign body sensation (highest rate at 3 months: 1.5%, 5/328), corneal erosion (also reported as AEs; cumulative rate of 0.9%; 3/334) and peripheral corneal epithelial defect (cumulative rate of 0.9%; 3/334). Transient light sensitivity syndrome was not reported at any time. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 20 {20} **Summary of Complications Over Time – All Eyes** | Complication | 1 Week to <1 Month (N=334) | | 1 Month (N=332) | | 3 Months (N=328) | | 6 Months (N=322) | | 9 Months (N=228) | | 12 Months (N=184) | | Cumulative^{a} (N=334) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | Corneal edema between 1 week and 1 month after the procedure | 116^{b} | 34.7 | | | | | | | | | | | | | | Peripheral corneal epithelial defect at 1 month or later | | | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 3 | 0.9 | | Corneal erosion at 1 month or later | | | 0 | 0.0 | 0 | 0.0 | 1 | 0.3 | 0 | 0.0 | 0 | 0.0 | 3^{c} | 0.9 | | Foreign body sensation at 1 month or later | | | 0 | 0.0 | 5 | 1.5 | 2 | 0.6 | 1 | 0.4 | 0 | 0.0 | 10 | 3.0 | | Pain at 1 month or later | | | 5 | 1.5 | 9 | 2.7 | 11 | 3.4 | 1 | 0.4 | 0 | 0.0 | 28 | 8.4 | | Ghost/diplopia (PRSVQ PRO)^{d} | 74 | 44.3 | 47 | 28.3 | 15 | 9.1 | 7 | 4.3 | 4 | 3.5 | 2 | 2.2 | 96 | 57.5 | | Transient light sensitivity syndrome | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | Note: Shaded blank areas represent time frames outside complication definition. % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N). $^{a}$ Cumulative includes unscheduled visits. $^{b}$ Between 1 week and 1 month, there were 96 Grade 1 reports, 14 Grade 2 reports, two Grade 3 reports, and 4 reports of edema being present, but the rating was not recorded. $^{c}$ Reported as a serious and/or device-related adverse events; Two cases documented as SADEs, one of which occurred and was treated by a primary care doctor between the 1- and 3-month study visits (no associated medical finding available at the time of occurrence); the other case was noted as corneal erosion at the time of occurrence (6 months). A third case was documented as an ADE with the medical finding of epithelial defect at an unscheduled visit between 3 and 6 months. $^{d}$ Complications based on subject-based PRVSQ Question 5a “Over the last 7 days, how often did you experience multiple or double vision?”. The n-values over time are as follows: n=167 at <1 month; n=166 at 1 month; n=164 at 3 months; n=161 at 6 months; n=114 at 9 months; n=92 at 12 months; n=167 for cumulative) PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 21 {21} # i) *Intraoperative Complications* All treated eyes (100.0%, 334/334) underwent uneventful treatment procedures with no intraoperative complications. Of the 334 treated eyes, most eyes (95.8%, 320/334) were treated with iris registration engaged for the duration of treatment. Fourteen eyes (4.2%, 14/334) underwent treatment without iris registration engaged across three sites. # j) *Patient Reported Outcomes (PRO) Measures and Questionnaires (PRVSQ for PRK/LASIK, NEI-RQL-42, OSDI, and Patient Satisfaction )* The results of the Patient Reported Visual Symptom Questionnaire (PRVSQ) PRO (**Table 11**), National Eye Institute Refractive Error Quality of Life Instrument (NEI-RQL) (**Table 12**), Ocular Surface Disease Index (OSDI) (**Table 13** and **Table 14**), and patient satisfaction with vision (**Table 15**) are shown on the next pages. The PRVSQ questionnaire asked patients to rank the frequency (never, rarely, sometimes, often, always) and level of bother ('not bothered', 'slightly', 'moderately', 'very', 'extremely') of their visual symptoms over the last 7 days. The results of the PRVSQ at 6 months (**Table 11**) indicated that the most reported visual symptom was sensitivity to light (55.9%; 90/161) followed by starbursts (35.4%; 57/161), glare (33.5%; 54/161), halos (26.7%; 43/161), fluctuating vision (18%; 29/161) and multiple/double vision (4.3%; 7/161). Overall, however, most subjects ($\geq 90\%$) were either not bothered or slightly bothered by symptoms or did not experience the visual symptom. There were no reports of extreme bother with any symptom at 6 months. Mean scores from the NEI-RQL (**Table 12**) are presented at preoperative and 6 months across all measures. OSDI questionnaire within-subject category status change (**Table 14**) shows that the majority of subjects that were Normal at preoperative remained Normal at 6 months. Most subjects (98.8%; 159/161) indicated being 'completely' or 'very' satisfied when asked to rate their overall satisfaction with present vision at 6 months (**Table 15**). PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 22 {22} **TABLE 11** **PRVSQ Optical Visual Symptoms All Subjects at 6 Months$^{a}$: Key Results** | Symptom | Percentage of subjects experiencing^{b} | Percentage of subjects often/always experiencing | Percentage of subjects did not experience^{c} or not bothered or slightly bothered | Highest bother rating and percentage of subjects | Percentage of subjects with limitation/difficulty | | --- | --- | --- | --- | --- | --- | | Halos | 26.7% (43/161) | 3.1% (5/161) | 99.4% (160/161) | Moderate 0.6% (1/161) | 0.6% (1/161) | | Glare | 33.5% (54/161) | 2.5% (4/161) | 96.3% (155/161) | Moderate 3.7% (6/161) | 0.6% (1/161) | | Starbursts^{d} | 35.4% (57/161) | 4.9% (8/161) | 96.3% (155/161) | Moderate 3.7% (6/161) | 0.0% (0/161) | | Sensitivity to Light | 55.9% (90/161) | 8.7% (14/161) | 90.0% (145/161) | Very 1.9% (3/161) | 3.7% (6/161) | | Multiple/Double Vision | 4.3% (7/161) | 0% (0/161) | 99.4% (160/161) | Moderate 0.6% (1/161) | 0.0% (0/161) | | Fluctuating Vision | 18.0% (29/161) | 1.2% (2/161) | 98.1% (158/161) | Moderate 1.9% (3/161) | 2.5% (4/161) | $^{a}$ The questionnaire asked patients to rank the frequency and level of bother of their visual symptoms over the last 7 days both before and at 6 months after treatment. $^{b}$ Total subjects indicating rarely, sometimes, often and always experiencing the given symptom $^{c}$ Includes subjects that did not experience the symptom or not reported. $^{d}$ One subject not reported **TABLE 12** **Mean Scores of NEI-RQL-42 Questionnaire Measures** **6 Month vs Preoperative (N=161 Subjects)** | Measure | Preoperative | 6 Month | | --- | --- | --- | | Clarity of vision | 87.86 | 94.00 | | Expectations | 4.35 | 91.15 | | Near vision | 74.26 | 91.91 | | Far vision | 83.60 | 96.94 | | Diurnal fluctuations | 88.72 | 95.73 | | Activity limitations | 54.90 | 98.95 | | Glare | 77.80 | 86.02 | | Symptoms | 87.79 | 89.06 | | Dependence on correction | 39.93 | 97.88 | | Worry | 44.57 | 85.71 | | Suboptimal correction | 95.50 | 99.92 | | Appearance | 38.96 | 96.65 | | Satisfaction with correction | 62.36 | 95.78 | NEI-RQL scores range from 0 to 100, higher scores represent better health. The changes in scores may not necessarily represent a clinically meaningful improvement or worsening in the NEI-RQL scores. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 23 {23} **OSDI Dry Eye Severity Categories Over Time – All Subjects** | OSDI Severity Category (scores) | Preoperative (N=167) | | 1 Month (N=166) | | 3 Month (N=164) | | 6 Month (N=161) | | 9 Month (N=114) | | 12 Month (N=92) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | | Normal (0-12) | 138 | 82.6 | 95 | 57.2 | 132 | 80.5 | 140 | 87.0 | 107 | 93.9 | 86 | 93.5 | | Mild (13-22) | 13 | 7.8 | 32 | 19.3 | 22 | 13.4 | 13 | 8.1 | 6 | 5.3 | 5 | 5.4 | | Moderate (23-32) | 6 | 3.6 | 19 | 11.4 | 8 | 4.9 | 5 | 3.1 | 0 | 0.0 | 0 | 0.0 | | Severe (33-100) | 10 | 6.0 | 20 | 12.0 | 2 | 1.2 | 3 | 1.9 | 1 | 0.9 | 1 | 1.1 | % Percentage is calculated by dividing the number of subjects in the cell (n) / by the total number of subjects per time period (N). **OSDI Within-Subject Category Status Change from Preoperative to 6 months** | Preoperative OSDI Status | 6M OSDI Status | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Normal | | Mild | | Moderate | | Severe | | Total | | | | n | % | n | % | n | % | n | % | n | % | | Normal | 123 | 90 | 9 | 7 | 3 | 2 | 1 | 1 | 136 | 100 | | Mild | 8 | 67 | 4 | 33 | 0 | 0 | 0 | 0 | 12 | 100 | | Moderate | 4 | 80 | 0 | 0 | 0 | 0 | 1 | 20 | 5 | 100 | | Severe | 6 | 67 | 0 | 0 | 2 | 22 | 1 | 11 | 9 | 100 | % Percentage is calculated by dividing the number of subjects in the cell (n) / by the total number of subjects per category (N). PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 24 {24} **Patient Satisfaction with Visual Quality – All Subjects** | Category | Satisfaction | Preop (N=167)^{a} | | 1 Month (N=166) | | 3 Month (N=164) | | 6 Month (N=161) | | 9 Month (N=114)^{b} | | 12 Month (N=92) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | n | % | n | % | n | % | n | % | n | % | n | % | | Q1. Please rate your satisfaction with your present vision when not wearing glasses or contacts | Completely satisfied | 0 | 0.0 | 59 | 35.5 | 117 | 71.3 | 127 | 78.9 | 91 | 79.8 | 80 | 87.0 | | | Very satisfied | 0 | 0.0 | 77 | 46.4 | 42 | 25.6 | 32 | 19.9 | 22 | 19.3 | 9 | 9.8 | | | Somewhat satisfied | 0 | 0.0 | 24 | 14.5 | 4 | 2.4 | 1 | 0.6 | 0 | 0.0 | 2 | 2.2 | | | Neither satisfied or dissatisfied | 2 | 1.2 | 1 | 0.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | | Somewhat dissatisfied | 14 | 8.4 | 4 | 2.4 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | | Very dissatisfied | 57 | 34.1 | 1 | 0.6 | 0 | 0.0 | 0 | 0.0 | 1 | 0.9 | 1 | 1.1 | | | Completely dissatisfied | 94 | 56.3 | 0 | 0.0 | 1 | 0.6 | 1 | 0.6 | 0 | 0.0 | 0 | 0.0 | | Q2. Please rate your satisfaction with your present vision when wearing glasses or contacts | Completely satisfied | 22 | 13.2 | 7 | 4.2 | 7 | 4.3 | 10 | 6.2 | 9 | 7.9 | 4 | 4.3 | | | Very satisfied | 64 | 38.3 | 9 | 5.4 | 1 | 0.6 | 4 | 2.5 | 4 | 3.5 | 1 | 1.1 | | | Somewhat satisfied | 61 | 36.5 | 6 | 3.6 | 5 | 3.0 | 0 | 0.0 | 1 | 0.9 | 1 | 1.1 | | | Neither satisfied or dissatisfied | 10 | 6.0 | 1 | 0.6 | 2 | 1.2 | 1 | 0.6 | 0 | 0.0 | 0 | 0.0 | | | Somewhat dissatisfied | 8 | 4.8 | 2 | 1.2 | 1 | 0.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | | Very dissatisfied | 3 | 1.8 | 4 | 2.4 | 1 | 0.6 | 2 | 1.2 | 1 | 0.9 | 2 | 2.2 | | | Completely dissatisfied | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 1.1 | | | Not applicable, I never wear glasses or contacts | 0 | 0.0 | 137 | 82.5 | 147 | 89.6 | 144 | 89.4 | 98 | 86.0 | 83 | 90.2 | | Q3. Please rate your OVERALL satisfaction with your present vision | Completely satisfied | 6 | 3.6 | 59 | 35.5 | 116 | 70.7 | 128 | 79.5 | 94 | 82.5 | 79 | 85.9 | | | Very satisfied | 21 | 12.6 | 79 | 47.6 | 44 | 26.8 | 31 | 19.3 | 19 | 16.7 | 11 | 12.0 | | | Somewhat satisfied | 59 | 35.3 | 24 | 14.5 | 3 | 1.8 | 1 | 0.6 | 0 | 0.0 | 1 | 1.1 | | | Neither satisfied or dissatisfied | 20 | 12.0 | 1 | 0.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | | Somewhat dissatisfied | 32 | 19.2 | 3 | 1.8 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | | Very dissatisfied | 15 | 9.0 | 0 | 0.0 | 0 | 0.0 | 1 | 0.6 | 1 | 0.9 | 1 | 1.1 | | | Completely dissatisfied | 14 | 8.4 | 0 | 0.0 | 1 | 0.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | % Percentage is calculated by dividing the number of subjects in the cell (n) / by the total number of subjects per time period (N). Cumulative including unscheduled visit. $^{a}$ At the preoperative visit, one subject marked two answers for Question 2: “Neither satisfied or dissatisfied” and “Somewhat dissatisfied” $^{b}$ At the 9-month visit, one subject did not mark an answer for Question 2. “n” represents total number of subjects. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 25 {25} # k) Contrast Sensitivity The changes in monocular best corrected contrast sensitivity from preoperative to 6 months using a non-parametric approach are presented in Table 16. At 6 months, median increases in contrast sensitivity from preoperative ranged between 0.07 and 0.14 log units under mesopic without glare conditions, between 0.04 and 0.16 log units under mesopic with glare conditions, and between 0.07 to 0.15 log units under photopic without glare conditions. Under all three lighting conditions, median changes in contrast sensitivity vs. preoperative were positive, indicating an increase (improvement) in contrast sensitivity postoperatively. TABLE 16 Contrast Sensitivity Change (Log Units) from Preoperative to 6 Months Using Non-Parametric Analysis (N=72 Eyes) | Lighting Condition | Spatial Frequency | Mean | SD | 25th Percentile | Median 50th Percentile | 75th Percentile | | --- | --- | --- | --- | --- | --- | --- | | Mesopic without glare | 1.5 cpd | 0.10 | 0.19 | 0.00 | 0.07 | 0.22 | | | 3.0 cpd | 0.10 | 0.23 | 0.00 | 0.14 | 0.23 | | | 6.0 cpd | 0.14 | 0.19 | 0.00 | 0.08 | 0.25 | | | 12.0 cpd | 0.11 | 0.33 | -0.08 | 0.08 | 0.26 | | Mesopic with glare | 1.5 cpd | 0.04 | 0.20 | -0.07 | 0.04 | 0.19 | | | 3.0 cpd | 0.08 | 0.22 | -0.07 | 0.07 | 0.15 | | | 6.0 cpd | 0.13 | 0.24 | 0.00 | 0.08 | 0.29 | | | 12.0 cpd | 0.17 | 0.35 | -0.07 | 0.16 | 0.35 | | Photopic without glare | 3.0 cpd | 0.08 | 0.20 | -0.07 | 0.07 | 0.22 | | | 6.0 cpd | 0.12 | 0.20 | 0.00 | 0.14 | 0.23 | | | 12.0 cpd | 0.18 | 0.32 | -0.00 | 0.15 | 0.40 | | | 18.0 cpd | 0.15 | 0.37 | -0.09 | 0.15 | 0.35 | # l) Higher Order Aberrations As shown in Table 17, analyses of higher order aberration (HOA) at 5 mm standardized wavefront diameter showed that HOA root mean square (RMS) minimally increased postoperatively. The small increase in total HOA RMS was associated with small increases in mean coma (ranging from 0.01 to 0.04 μm) and mean spherical aberration (0.02 μm). PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 26 {26} **TABLE 17** Preoperative and 6-month Higher Order Aberrations (HOA) (μm) Eyes with 5 mm Standardized Wavefront Diameters | | Preoperative (N=326) Mean +/- SD | 6 Months (N=302) Mean +/- SD | | --- | --- | --- | | **Total HOA RMS** | 0.16 +- 0.05 | 0.19 +- 0.08 | | **Coma** | 0.10 +- 0.05 | 0.12 +- 0.08 | | **Trefoil** | 0.08 +- 0.05 | 0.07 +- 0.04 | | **Spherical Aberration** | 0.05 +- 0.03 | 0.07 +- 0.06 | m) *Schirmer I Tear Test* At 6 months, the mean Schirmer score was 20.79 mm (SD 9.31), and the mean change in Schirmer score from preop was 0.11 mm (SD 7.73). At 6 months, 89.7% (288/322) had Schirmer scores of ≥10 mm (normal) and 3.4% (11/322) eyes had Schirmer scores of ≤5 mm (severe dryness; **Table 18**); however, there were no AEs of dry eyes (predefined as a Schirmer score of ≤ 5 mm at 3 months or later and an OSDI score of ≥33). **TABLE 18** Schirmer Score Distribution Over Time – All Eyes | | Preoperative (N=334) | | 3 Month (N=328) | | 6 Month (N=322) | | 12 Month (N=184) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | | **≤5 mm (severe dry)** | 8 | 2.4 | 13 | 4.0 | 11 | 3.4 | 6 | 3.3 | | **>5 mm to <10 mm** | 33 | 9.9 | 27 | 8.2 | 23 | 6.9 | 24 | 13.0 | | **≥10 mm (normal)** | 293 | 87.7 | 288 | 87.8 | 288 | 89.7 | 154 | 83.7 | % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N). n) *Additional Anterior Segment Evaluation Findings* The anterior segment was also evaluated for corneal clarity (**Table 19**) and changes in IOP. At 6 months, most eyes were noted with clear corneal clarity (score of 0) (90.1%; 290/322), 7.8% of eyes (25/322) were noted with faint/trace haze (score of 0.5), 1.9% (6/322) of eyes had mild haze (score of 1), and 1 eye (0.3%) had moderate haze (score of 2). At 6 months, the mean IOP was 12.33 mmHg (SD 2.05), and most eyes (90.1%; 290/322) had no change or decrease in IOP compared to preoperative. No eyes had an IOP >30 mmHg at any visit. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 27 {27} **Corneal Clarity Over Time – All Eyes** | Corneal Clarity (Grade) | Preop (N=334) | | 1 Day (N=334) | | 1 Week (N=334) | | 1 Month (N=332) | | 3 Month (N=328) | | 6 Month (N=322) | | 9 Month (N=228) | | 12 Month (N=184) | | Cumulative (N=334) | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | n | % | n | % | n | % | n | % | | Clear (0) | 332 | 99.4 | 321 | 96.1 | 311 | 93.1 | 295 | 88.9 | 275 | 83.8 | 290 | 90.1 | 212 | 93.0 | 176 | 95.7 | 334 | 100.0 | | Faint/Trace Haze (0.5) | 2 | 0.6 | 13 | 3.9 | 21 | 6.3 | 35 | 10.5 | 51 | 15.5 | 25 | 7.8 | 12 | 5.3 | 8 | 4.3 | 90 | 26.9 | | Mild Haze (1) | 0 | 0.0 | 0 | 0.0 | 2 | 0.6 | 2 | 0.6 | 2 | 0.6 | 6 | 1.9 | 4 | 1.8 | 0 | 0.0 | 11 | 3.3 | | Moderate Haze (2) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1^{a} | 0.3 | 0 | 0.0 | 0 | 0.0 | 1 | 0.3 | | Dense Haze; Opacity prevents refraction; AC visible (3) | 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 | | Dense Haze: Anterior chamber not visible (4) | 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 | | --Haze present, but rating not recorded | 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 | % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N) [ = (n/N).x 100%] Cumulative including unscheduled visit. $^{a}$ This eye had moderate haze (score of 2) and a loss of >2 lines of BSCVA that was reported as a serious, device-related adverse event. Preoperative BSCVA for this eye was 20/16 (LogMAR -0.14); at 6 months, BSCVA was 20/25 (LogMAR 0.14). At the 9-month visit, corneal haze was noted as mild and BSCVA had returned to 20/16 (LogMAR -0.14) PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 28 {28} o) Device Failures and Replacements There were no iDESIGN® System failures during the course of this study. Three iDESIGN® Systems were returned due to inconsistencies with the patient fixation and target appearance and brightness. These inconsistencies did not have any impact on the safety or effectiveness in this population as treatment plans in the study required strict agreement between iDESIGN® system and manifest refractions. 2. Effectiveness Results The analysis of effectiveness was based on 322 eyes at the 6-month time point. Key effectiveness outcomes are presented in Table 20. a) Greater than or equal to 85% of eyes have UCVA of 20/40 or better: At 6 months, the primary study endpoint of UCVA of 20/40 or better was achieved in 100% (322/322) of eyes monocularly, exceeding the endpoint target of 85% of eyes with 20/40 or better UCVA. Overall, the proportions of eyes that achieved UCVA of 20/40 or better exceeded the target rate (85%) at all postoperative study visits. b) Greater than or equal to 50% of eyes have MRSE within 0.50 D of intended correction: At 6 months, the point of refractive stability, 85.4% (275/322) of eyes had an MRSE within 0.50 D of target (emmetropia), exceeding the study endpoint target of ≥ 50% within 0.50 D. c) Greater than or equal to 75% of eyes have MRSE within 1.00 D of intended correction: At 6 months, the point of refractive stability, 96.3% (310/322) of eyes had an MRSE within 1.00 D, exceeding the study endpoint target of ≥ 75% within 1.00 D. TABLE 20 Summary of Key Effectiveness Endpoints Over Time – All Eyes | Effectiveness Variable | 1 Month (N=332) | | 3 Months (N=328) | | 6 Months (N=322) | | 9 Months (N=228) | | 12 Months (N=184) | | Target | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | % | n | % | n | % | n | % | n | % | | | UCVA 20/40 or better^{a} | 328 | 98.8% | 328 | 100% | 322 | 100% | 228 | 100% | 184 | 100% | ≥85% | | MRSE +/- 0.50 D^{b} | 223 | 67.2% | 274 | 83.5% | 275 | 85.4% | 185 | 81.1% | 157 | 85.3% | ≥50% | | MRSE +/- 1.00 D^{c} | 310 | 93.4% | 316 | 96.3% | 310 | 96.3% | 221 | 96.9% | 182 | 98.9% | ≥75% | % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N) [ = (n/N).x 100%]. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 29 {29} The key effectiveness endpoints at 6 months stratified by preoperative IDSE, IDS, and IDC are presented in **Tables 21-23**. The key effectiveness variables at 6 months stratified by preoperative IDC are presented in **Table 23**. All preoperative IDC diopter bins achieved the effectiveness endpoint targets PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 30 {30} **Effect of Preoperative iDesign Spherical Equivalent (IDSE) Groups at 6 Months** | Safety/Effectiveness Endpoints | Preoperative IDSE | Total (N=322) | Target | | --- | --- | --- | --- | | ≥-1.0 D to ≤0.0 D (n=5) | ≥-2.0 D to <-1.0 D (n=46) | ≥-3.0 D to <-2.0 D (n=54) | ≥-4.0 D to <-3.0 D (n=74) | ≥-5.0 D to <-4.0 D (n=36) | ≥-6.0 D to <-5.0 D (n=44) | ≥-7.0 D to <-6.0 D (n=33) | ≥-8.0 D to <-7.0 D (n=19) | ≥-9.0 D to <-8.0 D (n=11) | n | % | | n | % | n | % | n | % | n | % | n | % | n | % | n | | UCVA 20/40 or better | 5 | 100% | 46 | 100% | 54 | 100% | 74 | 100% | 36 | 100% | 44 | 100% | 33 | 100% | | MRSE +/- 0.50 D | 5 | 100% | 42 | 91.3% | 52 | 96.3% | 66 | 89.2% | 36 | 100% | 34 | 77.3% | 22 | 66.7% | | MRSE +/- 1.00 D | 5 | 100% | 46 | 100% | 54 | 100% | 73 | 98.6% | 36 | 100% | 39 | 88.6% | 32 | 97.0% | | BSCVA Worse than 20/40 | 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% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 3.0% | 0 | 0.0% | | Haze with Loss of >2 Lines BSCVA* | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 3.0% | 0 | 0.0% | | Induced Astigmatism >2D | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Serious Device related AE: Corneal Infiltration | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 2.8% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Serious Device related AE: Corneal Erosion | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 2.3% | 1 | 3.0% | 0 | 0.0% | PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 31 {31} | Preoperative IDSE | | --- | | Safety/Effectiveness Endpoints | ≥-1.0 D to ≤0.0 D (n=5) | ≥-2.0 D to <-1.0 D (n=46) | ≥-3.0 D to <-2.0 D (n=54) | ≥-4.0 D to <-3.0 D (n=74) | ≥-5.0 D to <-4.0 D (n=36) | ≥-6.0 D to <-5.0 D (n=44) | ≥-7.0 D to <-6.0 D (n=33) | ≥-8.0 D to <-7.0 D (n=19) | ≥-9.0 D to <-8.0 D (n=11) | Total (N=322) | Target | | n % | n % | n % | n % | n % | n % | n % | n % | n % | n % | n % | | Serious Device related AE: Corneal Haze | 0 0.0% | 0 0.0% | 0 0.0% | 0 0.0% | 0 0.0% | 0 0.0% | 1 3.0% | 0 0.0% | 2 18.2% | 3 0.9% | <1% | | Percentages calculated based on non-missing values. | | *Defined as change in logMAR >0.24. | **TABLE 22** **Outcomes Stratification Analysis** **Effect of Preoperative iDesign Preoperative iDesign Sphere (IDS) Groups at 6 Months** | Preoperative IDS | | --- | | Safety/Effectiveness Endpoints | ≥-1.0 D to ≤0.0 D (n=22) | ≥-2.0 D to <-1.0 D (n=64) | ≥-3.0 D to <-2.0 D (n=59) | ≥-4.0 D to <-3.0 D (n=54) | ≥-5.0 D to <-4.0 D (n=40) | ≥-6.0 D to <-5.0 D (n=37) | ≥-7.0 D to <-6.0 D (n=27) | ≥-8.0 D to <-7.0 D (n=19) | Total (N=322) | Target | | | n % | n % | n % | n % | n % | n % | n % | n % | n % | n % | | UCVA 20/40 or better | 22 100% | 64 100% | 59 100% | 54 100% | 40 100% | 37 100% | 27 100% | 19 100% | 322 100% | ≥85% | | | MRSE +/- 0.50 D | 20 90.9% | 61 95.3% | 54 91.5% | 48 88.9% | 36 90.0% | 26 70.3% | 18 66.7% | 12 63.2% | 275 85.4% | ≥50% | | PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 32 {32} | Safety/Effectiveness Endpoints | Preoperative IDS | Total (N=322) | Target | | --- | --- | --- | --- | | ≥-1.0 D to ≤0.0 D (n=22) | ≥-2.0 D to <-1.0 D (n=64) | ≥-3.0 D to <-2.0 D (n=59) | ≥-4.0 D to <-3.0 D (n=54) | ≥-5.0 D to <-4.0 D (n=40) | ≥-6.0 D to <-5.0 D (n=37) | ≥-7.0 D to <-6.0 D (n=27) | ≥-8.0 D to <-7.0 D (n=19) | | | n | % | n | % | n | % | n | % | n | % | n | % | | MRSE +/- 1.00 D | 22 | 100% | 64 100% | 59 100% | 51 94.4% | 39 97.5% | 35 94.6% | 24 88.9% | 16 84.2% | 310 96.3% | | ≥75% | | BSCVA Worse than 20/40 | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | <1% | | Loss of >2 Lines BSCVA* | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 0.0% | 0 | 1.0% | | <5% | | Haze with Loss of >2 Lines BSCVA* | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 0.0% | 0 | 1.0% | | <1% | | Induced Astigmatism >2D | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | <5% | | Serious Device related AE: Corneal Infiltration | 0 | 0.0% | 0 | 0.0% | 0 | 1.5% | 0 | 0.0% | 0 | 0.0% | | <1% | | Serious Device related AE: Corneal Erosion | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 2 | 0.0% | 0 | 0.0% | | <1% | | Serious Device related AE: Corneal Haze | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 0.0% | 2 | 10.5% | | <1% | | Percentages calculated based on non-missing values. *Defined as change in logMAR >0.24. | PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 33 {33} **Outcomes Stratification Analysis Effect of Preoperative iDesign Cylinder (IDC) Groups at 6 Months** | Safety/Effectiveness Endpoints | Preoperative IDC | | | | | | | | | | Total (N=322) | Target | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | ≥-0.5 D to ≤0.0 D (n=99) | | ≥-1.0 D to <-0.5 D (n=94) | | ≥-2.0 D to <-1.0 D (n=86) | | ≥-3.0 D to <-2.0 D (n=29) | | ≥-4.0 D to <-3.0 D (n=14) | | | | | | n | % | n | % | n | % | n | % | n | % | | | | UCVA 20/40 or better | 99 | 100% | 94 | 100% | 86 | 100% | 29 | 100% | 14 | 100% | 322 | 100% | | MRSE +/- 0.50 D | 85 | 85.9% | 85 | 90.4% | 71 | 82.6% | 24 | 82.8% | 10 | 71.4% | 275 | 85.4% | | MRSE +/- 1.00 D | 97 | 98.0% | 91 | 96.8% | 82 | 95.3% | 28 | 96.6% | 12 | 85.7% | 310 | 96.3% | | BSCVA Worse than 20/40 | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Loss of >2 Lines BSCVA* | 1 | 1.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 0.3% | | Haze with Loss of >2 Lines BSCVA* | 1 | 1.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 0.3% | | Induced Astigmatism >2D | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | | Serious Device related AE: Corneal Infiltration | 0 | 0.0% | 1 | 1.1% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 1 | 0.3% | | Serious Device related AE: Corneal Erosion | 1 | 1.0% | 1 | 1.1% | 0 | 0.0% | 0 | 0.0% | 0 | 0.0% | 2 | 0.6% | | Serious Device related AE: Corneal Haze | 1 | 1.0% | 0 | 0.0% | 2 | 2.3% | 0 | 0.0% | 0 | 0.0% | 3 | 0.9% | Percentages calculated based on non-missing values. *Defined as change in logMAR &gt;0.24. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 34 {34} # d) UCVA **Table 24** presents monocular UCVA outcomes over time. At 6 months, the point of refractive stability, 100% (322/322) of eyes had UCVA of 20/40 or better and 99.4% (320/322) of eyes had UCVA of 20/20 or better. Similar information was provided for binocular UCVA (see **Table 25** below) PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 35 {35} **Monocular UCVA Over Time All Eyes** | LogMAR Value | Acuity | Preoperative (N=334) | 1 Month (N=332) | 3 Months (N=328) | 6 Months (N=322) | 9 Months (N=228) | 12 Months (N=184) | | --- | --- | --- | --- | --- | --- | --- | --- | | | | n % (95% CI) | n % (95% CI) | n % (95% CI) | n % (95% CI) | n % (95% CI) | n % (95% CI) | | ≤ -0.06 | 20/16 or better | 0 0.0% ( - , - ) | 171 51.5% (46.0, 57.0) | 290 88.4% (84.4, 91.7) | 296 91.9% (88.4, 94.7) | 208 91.2% (86.8, 94.6) | 175 95.1% (90.9, 97.7) | | ≤ 0.04 | 20/20 or better | 2 0.6% ( 0.1, 2.1) | 265 79.8% (75.1, 84.0) | 325 99.1% (97.4, 99.8) | 320 99.4% (97.8, 99.9) | 226 99.1% (96.9, 99.9) | 184 100% (98.4, 100) | | ≤ 0.14 | 20/25 or better | 3 0.9% ( 0.2, 2.6) | 314 94.6% (91.6, 96.8) | 328 100% (99.1, 100) | 320 99.4% (97.8, 99.9) | 227 99.6% (97.6, 100) | 184 100% (98.4, 100) | | ≤ 0.34 | 20/40 or better | 19 5.7% ( 3.5, 8.7) | 328 98.8% (96.9, 99.7) | 328 100% (99.1, 100) | 322 100% (99.1, 100) | 228 100% (98.7, 100) | 184 100% (98.4, 100) | | ≤ 0.74 | 20/100 or better | 96 28.7% (23.9, 33.9) | 332 100% (99.1, 100) | 328 100% (99.1, 100) | 322 100% (99.1, 100) | 228 100% (98.7, 100) | 184 100% (98.4, 100) | | > 0.74 | Worse than 20/100 | 238 71.3% (66.1, 76.1) | 0 0.0% ( - , - ) | 0 0.0% ( - , - ) | 0 0.0% ( - , - ) | 0 0.0% ( - , - ) | 0 0.0% ( - , - ) | | Not Reported | Not reported | 0 | 0 | 0 | 0 | 0 | 0 | Percentage is calculated based on non-missing values [ (n/N).x 100%]. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 36 {36} **Binocular UCVA Over Time Safety Population** | LogMAR Value | Acuity | Pre-Op (N=167) | 1 Month (N=166) | 3 Months (N=164) | 6 Months (N=161) | 9 Months (N=114) | 12 Months (N=92) | | --- | --- | --- | --- | --- | --- | --- | --- | | | | n % (95% CI) | n % (95% CI) | n % (95% CI) | n % (95% CI) | n % (95% CI) | n % (95% CI) | | <=-0.06 | 20/16 or better | 1 0.6% (0.0, 3.3) | 128 77.1% (70.0, 83.3) | 161 98.2% (94.7, 99.6) | 160 99.4% (96.6, 100) | 112 98.2% (93.8, 99.8) | 92 100% (96.8, 100) | | <= 0.04 | 20/20 or better | 3 1.8% (0.4, 5.2) | 155 93.4% (88.5, 96.6) | 164 100% (98.2, 100) | 161 100% (98.2, 100) | 114 100% (97.4, 100) | 92 100% (96.8, 100) | | <= 0.14 | 20/25 or better | 8 4.8% (2.1, 9.2) | 165 99.4% (96.7, 100) | 164 100% (98.2, 100) | 161 100% (98.2, 100) | 114 100% (97.4, 100) | 92 100% (96.8, 100) | | <= 0.34 | 20/40 or better | 27 16.2% (10.9, 22.6) | 166 100% (98.2, 100) | 164 100% (98.2, 100) | 161 100% (98.2, 100) | 114 100% (97.4, 100) | 92 100% (96.8, 100) | | <= 0.74 | 20/100 or better | 72 43.1% (35.5, 51.0) | 166 100% (98.2, 100) | 164 100% (98.2, 100) | 161 100% (98.2, 100) | 114 100% (97.4, 100) | 92 100% (96.8, 100) | | > 0.74 | Worse than 20/100 | 95 56.9% (49.0, 64.5) | 0 0.0% (- , -) | 0 0.0% (- , -) | 0 0.0% (- , -) | 0 0.0% (- , -) | 0 0.0% (- , -) | | Not Reported | Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | [a] Confidence Interval is calculated based on Clopper-Pearson Exact method. [b] Percentage is calculated based on non-missing values [(n/N).x 100%]. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 37 {37} Table 26 presents the differences in postoperative UCVA achieved compared to preoperative BSCVA. At 6 months, 81.4% (262/322) of eyes achieved the same or better acuity level postoperatively without correction as preoperatively with correction. TABLE 26 Postoperative Monocular UCVA Compared to Preoperative Monocular BSCVA All Eyes (N=332) | LogMAR Change | Acuity Change | 1 Month (N=332) n % | 3 Months (N=328) n % | 6 Months (N=322) n % | 9 Months (N=228) n % | 12 Months (N=184) n % | | --- | --- | --- | --- | --- | --- | --- | | <-0.24 | >2 lines better | 0 0.0% | 0 0.0% | 0 0.0% | 0 0.0% | 0 0.0% | | ≥-0.24 to <-0.14 | 2 lines better | 0 0.0% | 1 0.3% | 5 1.6% | 3 1.3% | 6 3.3% | | ≥-0.14 to <-0.04 | 1 line better | 16 4.8% | 62 18.9% | 88 27.3% | 76 33.3% | 70 38.0% | | ≥-0.04 to ≤0.04 | Equal | 91 27.4% | 197 60.1% | 169 52.5% | 117 51.3% | 91 49.5% | | >0.04 to ≤0.14 | 1 line worse | 131 39.5% | 61 18.6% | 55 17.1% | 27 11.8% | 14 7.6% | | >0.14 to ≤0.24 | 2 lines worse | 56 16.9% | 7 2.1% | 3 0.9% | 3 1.3% | 3 1.6% | | >0.24 | >2 lines worse | 38 11.4% | 0 0.0% | 2 0.6% | 2 0.9% | 0 0.0% | | Not Reported | | 0 | 0 | 0 | 0 | 0 | | % Percentage is calculated by dividing the number of eyes in the cell (n) / by the total number of eyes per time period (N). | | | | | | | # e) Accuracy of Manifest Refraction At 6 months post-operative, 85.4% (275/322) of eyes were within 0.50 D, and 96.3% (310/322) within 1.0 D of attempted correction (emmetropia). Table 27 presents the accuracy of MRSE over time for all treated eyes. At 6 months, 1 eye (0.3%; 1/322) was undercorrected >1.00 D and 11 eyes (3.4%; 11/322) were overcorrected >1.00 D, of which 1 eye (0.3%; 1/322) was overcorrected >2.00 D. PMA P930016/S057: FDA Summary of Safety and Effectiveness Data Page 38 {38} **TABLE 27** **Accuracy of MRSE: Intended vs. Achieved Outcome** | | Preoperative (N=334) | 1 Month (N=332) | 3 Months (N=328) | 6 Months (N=322) | 9 Months (N=228) | 12 Months (N=184) | | --- | --- | --- | --- | --- | --- | --- | | MRSE | n % (95% CI) | n % (95% C…