TECHNOLAS TENEO™ 317 (MODEL 2) Excimer Laser System

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION | Device Generic Name: | Ophthalmic Excimer Laser System | | --- | --- | | Device Trade Name: | TECHNOLAS TENEO™ 317 (MODEL 2) Excimer Laser System | | Device Procode: | LZS | | Applicant's Name and Address: | Bausch + Lomb Incorporated 1400 North Goodman Street Rochester, New York 14609 | | Date of Panel Recommendation: | N/A | | Premarket Approval (PMA) | P990027/S021 | | Application Number: | | | Date of FDA Notice of Approval: | November 22, 2023 | | Priority Review: | N/A | | Breakthrough Device: | N/A | The parent laser system, the TECHNOLAS 217A excimer laser system with Planoscan (PS) software (SW), PMA P990027, was approved on February 25, 2000 and was indicated for photorefractive keratectomy for the reduction or elimination of myopia ranging from -1.00 D to -7.00 D spherical myopia with our without 5 -3.00 astigmatism. The device then gained approval for expansion of the indication for laser in-situ keratomileusis (LASIK) treatments for the reduction or elimination of myopic astigmatism up to -12.0 D MRSE, with sphere between < -7.00D to -10.99 D and cylinder between 0.00 and <-3.00 Din P990027/S002. The SSED to support the indication is available on the CDRH website and is incorporated by reference here. The current supplement was submitted to expand the indications for the TECHNOLAS TENEO 317 MODEL2 US excimer laser system (TENEO 317). PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 1/65 {1} ## II. INDICATIONS FOR USE The TECHNOLAS TENEO 317 MODEL2 US is indicated for laser-assisted in situ keratomileusis (LASIK) in: - Patients for the reduction or elimination of myopic astigmatism up to -10.00 D MRSE, with sphere between -1.00 D to -10.0 D and cylinder between 0.00 and -3.00 D; - Patients who are 22 years of age or older; - Patients must have a stable refraction in the last 12 months, as documented by previous clinical recordings, i.e., the spherical and cylindrical portions of the manifest distance refraction have not progressed at a rate of more than 0.50 D per year prior to the baseline examination in the eye(s) to be treated. ### III. CONTRAINDICATIONS TECHNOLAS TENEO 317 MODEL2 US driven LASIK surgery is contraindicated in: - Patients with any type of active connective tissue disease or autoimmune disease - Patients with signs of keratoconus, abnormal corneal topography, and degenerations of the structure of the cornea (including but not limited to pellucid marginal degeneration) - Patients with significant dry eyes (severe Dry Eye Syndrome). - If 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. - Patients for whom the combination of their baseline corneal thickness and the planned operative parameters for the LASIK procedure would result in less than 250 μm of residual corneal thickness from corneal endothelium. - Patients with uncontrolled diabetes - Patients with uncontrolled glaucoma - Patients with active eye infection or active inflammation - Patients with recent herpes eye infection or problems resulting from past infection - Patients with known sensitivity to medications used for standard LASIK surgery ### IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the TECHNOLAS TENEO 317 MODEL2 US excimer laser system labeling. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 2/65 {2} ## V. DEVICE DESCRIPTION The TECHNOLAS TENEO 317 MODEL2 US Laser System is an Excimer Laser System operating at a wavelength of 193 nm with a repetition rate of 500 Hz. The TECHNOLAS TENEO 317 MODEL2 US uses the interaction of pulsed laser beams of Ultraviolet light at 193nm wavelength with the human cornea. The spot size of the laser beam is controlled by an aperture and an optical device to shape the intensity profile of each spot into a truncated Gaussian beam shape. Each laser pulse will remove a small amount of tissue from the corneal or stromal surface. A high-precision scanner system directs each pulse to the predefined location. The combination of many individual pulses allows creating very precise, preprogrammed ablation patterns to reshape the cornea of the human eye, designed to treat a refractive error of the eye and improve the vision of the treated subject. Due to the high 500 Hz repetition rate of the TECHNOLAS TENEO 317 MODEL2 US the system can operate using a small spot size of 1mm while still performing the whole ablation in a sufficiently short timeframe. The laser offers additional aiming beams in the visible light range which allow the user to position the eye in height and lateral position, as well as to precisely register the desired treatment location of the eye. The operative microscope also supports the positioning of the eye. Furthermore, the TECHNOLAS TENEO 317 MODEL2 US implements a video based state-of-the-art multidimensional eye tracking system with a tracking speed adapted to the laser repetition rate. Lateral and rotational eye movement during the treatment is actively compensated by re-adjusting the treatment pattern accordingly. The parent laser system, the TECHNOLAS 217A excimer laser system for LASIK myopic indication with Planoscan (PS) software (SW), was originally approved by FDA via P990027 with the treatment range expanded via P990027/S002. Subsequently, FDA approved P990027/S018 for TECHNOLAS 217z Zyoptix with Advanced Planoscan (AdvPS) SW. Both the PS and AdvPS SW deliver a non-aspheric ablation profile. The key SW difference between the approved TECHNOLAS 217A PS/AdvPS treatment SW and the TECHNOLAS TENEO 317 MODEL2 US treatment SW is that the TECHNOLAS TENEO 317 MODEL2 US SW is designed to impart an aspheric ablation profile. Advanced features: - Beam path flushed with N2 - Plume evacuation - 360° swiveling surgical microscope - Spot size approximately 1 mm - Closed energy loop control (using three energy monitors) - Multidimensional high-speed eye tracking (eye tracker 1740 frames per second (fps)): - Tracks and simultaneously adjusts the ablation pattern for the entire duration of the procedure - Movements in X/Y direction and rotational movement of the patient's eye PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 3/65 {3} - Dynamic rotational tracking # **PROSCAN treatment** PROSCAN is based on the subjective refractive error of the eye intended to be treated for myopia with and without astigmatism and the intended optical zone. PROSCAN is an aspheric, non-customized (using population mean K- and Q-value) ablation profile. # **VI. ALTERNATIVE PRACTICES AND PROCEDURES** There are several other alternatives for the correction of myopia or myopic astigmatism: - Glasses or Contact Lenses - Standard Photo Refractive Keratectomy (PRK) or LASIK - Wavefront-guided or corneal topography-assisted LASIK or PRK - Refractive Lenticule Extraction (ReLEx) - Implantable lens surgery (phakic Intraocular Lens) 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 TECHNOLAS TENEO 317 MODEL2 US excimer laser systems have been distributed in over 55 countries including Algeria, Argentina, Armenia, Austria, Azerbaijan, Belgium, Brazil, Canada, Chile, Czech Republic, Dominican Republic, Ecuador, Egypt, Finland, France, Georgia, Germany, Greece, Hong Kong, India, Indonesia, Iran, Iraq, Ireland, Israel, Italy, Korea, Kuwait, Lithuania, Malaysia, Mexico, Morocco, North Macedonia, Palestine, Peru, Philippines, Poland, Portugal, Romania, Russia, Saudi Arabia, Senegal, Serbia, Singapore, Slovenia, Spain, Switzerland, Taiwan, Thailand, Tunisia, Turkey, Ukraine, United Kingdom, and Uzbekistan. 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 device¹: Intraoperative complications: - Miscreated flap (lost, incomplete, too thin, misaligned, buttonhole, etc.) - Subconjunctival hemorrhage or bleeding Postoperative complications - Wrinkles in flap (striae) that may require a flap lift - Corneal erosion/abrasion, epithelial defect - Elevated IOP (e.g., steroid induced) - Debris or foreign body under flap ¹ Please note: The potential complication / side effects reported during use of the device are not related exclusively to the laser device itself. For example, subconjunctival hemorrhage are a common complication of LASIK, but is not related to the excimer device, but to the flap creating devices. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 4/65 {4} - Epithelial ingrowth under flap - Debilitating visual symptoms, especially at night time (glare, halo, starburst, ghost and double or multiple images, distortion, hazy or blurred vision, difficulty with night driving) - Decreased or fluctuating visual acuity (uncorrected and/or best corrected) - Decreased ability to see in low-light conditions (e.g., reading a street sign at dusk) - Light sensitivity (e.g. Transient light-sensitivity syndrome (TLSS)) - Dry Eye syndrome (surgically induced, or worsening of pre-existing signs and/or symptoms) - Inadequate treatment result, including (but not limited to): - Over-correction or under-correction, induced or residual astigmatism, may require eyeglass or contact lens wear - Decentered ablation - Anisometropia (imbalance between the two eyes that may cause headaches, eye strain, double vision and/or difficulty judging distance or depth perception) - Regression (reduction in the refractive correction over time) - Corneal damage: - Corneal ectasia (bulging) - Corneal edema (swelling) - Corneal haze - Corneal changes like anterior basement membrane dystrophy - Corneal scarring - Corneal decompensation - Corneal ulceration or perforation - Corneal infection or inflammation - Posterior Vitreous Detachment or Retinal Detachment (e.g. macular hole), floaters or vascular accidents - Foreign body sensation (feeling of grittiness or something in eye) or pain initial postoperative days); also, potentially including chronic eye pain that is resistant to therapy referred to as neuropathic pain - Infection/Inflammation (like corneal infiltrates, ulcer, DLK (Diffuse lamellar keratitis), SPK (Superficial punctate keratopathy), uveitis, lamellar keratitis, sterile inflammation, etc.) - CTK (Central Toxic Keratopathy) - Medication intolerance (increased intraocular pressure, allergically reaction, etc.) - Ptosis (drooping eyelid, may require surgical intervention) - Cataract - Ocular penetration - Potential risk of psychological harm Difficulties in future ophthalmic assessments: - After refractive surgery, there may be difficulties in future ophthalmic assessments, such as selecting an appropriate intraocular lens (IOL) for implantation during cataract surgery and assessing intraocular pressure (IOP). - It is recommended that physicians consider whether it may be useful to provide the patient their pre-operative values. - Patients around 40 years of age or older may need eyeglasses for close work such as PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 5/65 {5} reading due to presbyopia 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 ### A. Laboratory Studies N/A ### B. Animal Studies N/A ### C. Additional Studies A brief summary of nonclinical tests for the TENEO 317 (Model 2) laser is provided below: | Test | Purpose | Conclusion | Results | | --- | --- | --- | --- | | Repetition rate stability | Determination of stability of laser head repetition rate | These data demonstrate that the TECHNOLAS TENEO 317 (Model 2) delivers laser pulses at a frequency of 500 Hz. | PASS | | Energy Density (Fluence) at the Eye | Evaluation of treatment energy within 2-hour laser calibration interval | It is concluded that the TECHNOLAS TENEO 317 (Model 2) maintains a steady energy of 1.6 mJ (representing an energy density of 200 mJ/cm^{2}) throughout the recommended energy calibration interval. | PASS | | Laser Pulse Duration | Evaluation of pulse length measurements | The results demonstrate that the pulse duration for TECHNOLAS TENEO 317 remains within specifications. | PASS | | Accuracy of ablation profiles (spot positioning) | Evaluation of treatment pattern on porcine eyes | It was concluded that the differences between the intended versus achieved profile are within the acceptance criteria of 0.25 D, and therefore the TECHNOLAS TENEO 317 (Model 2) achieves intended ablation profiles with an accuracy of 0.25 D or better. | PASS | | Thermal effect control | Evaluation of corneal temperature rise of myopic ablation on porcine corneas | It was concluded that ablations with the TECHNOLAS TENEO 317 (Model 2) laser system do not pose a substantial risk to the cornea in terms of temperature increase. | PASS | | Hardware Validation | Employ a wide range of benchtop testing to ensure the safe and effective device function | Testing demonstrated validation of device housing modifications, eye tracker function, spot positioning accuracy, verification of the excimer laser source, verification of all aspects of the optical beam path, verification of the extremal energy monitor, verification of microscope operation, verification of the operational field illumination, verification if the component requirements of the scanner module, verification of the excimer computer unit, verification results of the Monitor Column, verification of the foot switch, plume suction, and rotating patient bed, and radiation safety. | PASS | | Software Validation | Evaluate the consistency, completeness, and correctness of the software and its supporting | The TECHNOLAS TENEO 317 (Model 2) laser system software has been designed, implemented, verified, and validated according with FDA recommendations. Additionally, the ablation algorithm has been reviewed and validated. Software validation has been provided in accordance with FDA guidance 'Guidance for the Content | PASS | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 6/65 {6} | Test | Purpose | Conclusion | Results | | --- | --- | --- | --- | | | documentation, confirm that the software development output meets its input requirements, review software architecture, software detailed design, and traceability analyses | of Premarket Submissions for Software Contained in Medical Devices”. | | | Cybersecurity Validation | Ensures safeguards against unauthorized device access, software modification, misuse, denial of use, and unauthorized use of information that is stored, accessed, or transferred | The TECHNOLAS TENEO 317 (Model 2) laser system software and hardware environment employ sufficient security safeguards against cyber and physical security attacks. Cybersecurity validation has been provided in accordance with FDA guidance “Content of Premarket Submissions for Management of Cybersecurity in Medical Devices” | PASS | | Electromagnetic safety and Compatibility | Ensure continuous device function in a noisy electromagnetic field environment | The results demonstrate that the TECHNOLAS TENEO 317 remains functional within specifications in the presence of a range of electromagnetic frequency signals and when subjected to electrostatic discharges. Testing has been performed in accordance with IEC 60601-1:2005 +AMD1:2012 + AMD2:2020; IEC 60601-1-2:2014 + AMD1:2020; and IEC 60601-2-22:2019. | PASS | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 7/65 {7} # X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the PROSCAN treatment algorithm with TECHNOLAS TENEO 317 MODEL2 US for the reduction or elimination of myopia and myopic astigmatism, up to -11.50 D manifest refraction spherical equivalent (MRSE) with sphere between -1.00 D to -10.0 D and cylinder between 0.00 and <-3.00 D, at sites in the US under IDE # G180286. Data from this clinical study are the basis for the PMA approval decision. A summary of the clinical study is presented below. # A. Study Design Patients were treated between July 30, 2019 and December 4, 2020. The database for this Panel Track Supplement reflected data collected through August 6, 2021 and included 333 eyes of 168 patients. There were 10 investigational sites. The study was a multicenter, prospective, open-label, nonrandomized, single-arm study evaluating the safety and effectiveness of the TENEO 317 (Model 2) when used in LASIK surgery to treat myopia or myopic astigmatism by comparing postoperative refraction and visual acuity to standard guidelines, as well as assessment of adverse events ant visual symptoms. The study design allowed for 6 follow-up visits over 9 months to allow subjects' vision to achieve refractive stability postoperatively. All study eye treatments were targeted for emmetropia. The Statistical Analysis Plan was written with due consideration of the recommendations outlined in the most recent International Conference on Harmonisation (ICH) E3 Guideline (July 1996), entitled Guidance for Industry: Structure and Content of Clinical Study Reports. # General Analysis Methods Summaries for continuous and ordinal variables included the number of observations (n), arithmetic mean, standard deviation, median, minimum, and maximum. Minima and maxima were reported with the same precision as the raw values; means and medians were presented to 1 additional decimal place than reported in the raw values. Standard deviations were presented to 2 additional decimal places than reported in the raw values. Summaries for discrete variables included counts and percentages. All percentages were rounded to 1 decimal place (ie, XX.X%). All statistical tests were one-sided with a significance level of 0.025 (α = 0.025) unless otherwise specified. Confidence intervals (CIs) around single estimated proportions were two-sided at 95% confidence. All p-values were rounded to 4 decimal places. Eyes were treated as independent sampling units. # Determination of Sample Size Prior clinical experience with the TENEO 317 (Model 2) in Europe showed that 94.5% of eyes were within 0.50 D and 99% of eyes were within 1.00 D of targeted MRSE 1 month after surgery. In addition, 100% of eyes achieved UCDVA of 20/40 or better at 1 month. - Percentage of Eyes That Achieve Predictability of MRSE Within ± 0.50 D at the Time of Refractive Stability: A one group χ² test with a 2.5% one-sided significance level had > 99.99% power to detect the difference between the null hypothesis proportion, π₀, of 0.80 and the alternative proportion, π₁, of 0.945 when the sample size was 300. - Percentage of Eyes That Achieve Predictability of MRSE Within ± 1.00 D at the Time of Refractive Stability: PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 8/65 {8} A one group χ² test with a 2.5% one-sided significance level had > 99.99% power to detect the difference between the null hypothesis proportion, π₀, of 0.90 and the alternative proportion, π₁, of 0.99 when the sample size was 300. - Percentage of Eyes Targeted for Emmetropia That Achieve uncorrected distance visual acuity (UCDVA) of 20/40 or Better at the Time of Refractive Stability: A one group χ² test with a 2.5% one-sided significance level had > 99.99% power to detect the difference between the null hypothesis proportion, π₀, of 0.88 and the alternative proportion, π₁, of 0.99 when the sample size was 300. ### 1. Clinical Inclusion and Exclusion Criteria There was one treatment group in this study. All subjects who met eligibility criteria were consecutively offered enrollment into the trial. Both eyes of a subject could be enrolled if they met eligibility requirements, but if an intraoperative complication or adverse event (AE) occurred in the first eye, treatment was to be abandoned in the second eye. Enrollment in the study was limited to patients who met the following inclusion criteria: - Are 22 years of age or older. - Have read, understood, and signed an ICF (Informed Consent Form). - Have demonstrated stable refraction (ie, a change of ≤ 0.5 D in sphere and cylinder) for a minimum of 12 months prior to surgery, verified by consecutive refractions and/or medical records or prescription history. - Have myopic refractive error with or without astigmatism; sphere between -1.0 D and -10.00 D, cylinder between 0.0 D and -3.0 D; with a manifest refraction spherical equivalent (MRSE) between -1.0 D and -11.50 D. - Have UCDVA of 20/40 or worse. - Have manifest best spectacle-corrected distance visual acuity (BSCVA) of 20/25 (logMAR 0.1) or better in an operative eye. - Have less than or equal to 0.50 D spherical equivalent (SE) difference between cycloplegic and manifest refractions at Visit 1 (Preoperative). - Have normal corneal topography as determined by the Investigator. - Have discontinued use of contact lenses for at least 2 weeks (for hard or toric lenses) or 3 days (for soft contact lenses) prior to the preoperative examination, and through the day of surgery. - All contact lens wearers must demonstrate a stable refraction (within ± 0.5 D), as determined by MRSE, on 2 consecutive examinations at least 1 week apart, in an eye to be treated and the axis of cylinder should not differ by more than 15 degrees. - Have the ability to lie flat without difficulty. - Are willing and able to comply with the schedule for all post-surgery follow-up visits. Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: - Subjects for whom the combination of their baseline corneal thickness and the planned operative parameters for the LASIK procedure would result in treatment depth less than 250 μm from corneal endothelium. - Eyes for which the baseline manifest subjective refraction exhibits a difference greater than 0.50 D in sphere power, or a difference greater than 0.50 D in cylinder power, or a difference in cylinder axis of more than 15 degrees compared to the baseline cycloplegic PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 9/65 {9} subjective refraction. For manifest cylinder of less than 0.50 D, the difference in cylinder axis will not be taken into consideration. - Subjects for whom the preoperative assessment of the cornea indicates that one or both eyes are not suitable candidates for treatment based upon the Investigator's medical judgment. - Have evidence of retinal vascular disease. - Have a history of or have active corneal disease or infection (e.g., recurrent corneal erosion syndrome, herpes simplex or herpes zoster keratitis, etc.) in an eye. - Have a known sensitivity to any study medication. - Have central corneal scars affecting visual acuity or unstable keratometry with irregular mires in an eye considered for eligibility. - Have keratoconus, subclinical or forme fruste keratoconus, corneal dystrophy, or other corneal irregularity (e.g., irregular astigmatism). - Have visually significant or progressive cataract in an eye considered for eligibility. - Had previous intraocular or corneal surgery in an eye considered for eligibility that might confound the outcome of the study or increase the risk to the subject. - Use chronic medications by any administration route that may increase risk to the subject or may confound the outcome of the study, including those known to affect wound healing (e.g., corticosteroids, antimetabolites, etc.). - Are known to have acute or chronic disease or illness (e.g., dry eye, cataract, glaucoma, immuno-compromised, rheumatoid arthritis, clinically significant atopic disease, acne rosacea, etc.) that would increase operative risk or may confound the results of the study. - Are taking medications contraindicated for LASIK such as isotretinoin (Accutane) or amiodarone hydrochloride (Cordarone). - Are known to be pregnant, lactating, or who plan to become pregnant during the course of the study. - Have known sensitivity to medications used for standard LASIK. - Have the presence of systemic disease likely to affect wound healing, e.g., autoimmune disease, systemic connective tissue disease, diabetes, or severe atopic disease. - Are participating in any other ophthalmic clinical trial within 30 days of screening or during this clinical trial. - Have an ocular muscle disorder including a strabismus or nystagmus, or other disorder affecting fixation. - Have a history of or evidence of glaucoma or are a glaucoma suspect. - Have eyes with mesopic pupil size > 7.0 mm. - Have a Schirmer's preoperative test without anesthesia < 4 mm/5 minutes ## 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations at: | Visit 1 | Pre-Op | (Day-60 to Day -1) | | --- | --- | --- | | Visit 2 | Operative Visit | (Day 0) | | Visit 3 | Day 1 | | | Visit 4 | Week 1 | (Day 5-9) | | Visit 5 | Month 1 | (Week 3-5) | | Visit 6 | Month 3 | (Week 10-14) | | Visit 7 | Month 6 | (Week 21-26) | | Visit 8 | Month 9 | (Week 35-43) | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 10/65 {10} The preoperative and postoperative objective parameters measured during the study are shown in Table 1. Table 1: preoperative and postoperative objective parameters of the study | PROCEDURE/ ASSESSMENTS | Visit 1 | Visit 2 | Visit 3^{1} | Visit 4 | Visit 5 | Visit 6 | Visit 7 | Visit 8 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Informed consent/HIPAA | X | | | | | | | | | Eligibility | X | X | | | | | | | | PROWL questionnaires^{2} | X | | | | | X | X | X | | Adverse events | X | X | X | X | X | X | X | X | | Complications | | X | X | X | X | X | X | X | | Subject demographics | X | | | | | | | | | Medical/Ocular history | X | | | | | | | | | Concomitant medications | X | X | X | X | X | X | X | X | | Schirmer's test^{3} | X | | | | | | X | | | LASIK surgery, | | X | | | | | | | | Manifest refraction | X | | | X | X | X | X | X | | Keratometry^{5} | X | | | | | | | | | ECD^{6} | X | | | | | | X | | | Corneal topography | X | | | | X | X | X | X | | Pupil size^{7} | X | | | | | X | X | X | | UCVNA^{9} | X | | X | X | X | X | X | X | | UCDVA^{8} | X | | X | X | X | X | X | X | | Distance BSCVA^{9} | X | | | X^{9} | X^{10} | X^{10,11} | X^{10,11} | X^{10,11} | | Contrast sensitivity | X | | | | | | X | | | Slit lamp examination^{11} | X | | X | X | X | X | X | X | | Pachymetry^{12} | X | | | | | | | | | Cycloplegic refraction | X | | | | | | | | | IOP^{13} | X | | | | X | X | X | X | | Dilated fundus exam | X | | | | | X^{14} | X^{14} | X^{14} | Abbreviations: BSCVA = best spectacle-corrected distance visual acuity; ECD = endothelial cell density; HIPAA = Health Insurance Portability and Accountability Act; IOP = intraocular pressure; LASIK = laser in situ keratomileusis; OD = right eye; OS = left eye; PROWL = Patient-Reported Outcomes With LASIK; UCDVA = uncorrected distance visual acuity; UCNVA = uncorrected near visual acuity. 1. The same parameters are to be measured at each examination performed until re-epithelialization occurs (when applicable). 2. The PROWL questionnaires 34, 35 should be completed by the study subject in a secluded area, free of directions from clinical staff, at Visit 6, 7, and 8. 3. The Schirmer's test must not be conducted with anesthesia. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 11/65 {11} 4. LASIK surgery is to be conducted by a refractive surgeon adequately trained by B+L or TPV technical representatives for use of the TENEO 317 (Model 2) and supervised by a technical representative for at least the first 4 LASIK surgeries completed by the refractive surgeon. 5. Keratometry should be assessed only at the preoperative study visit and as needed at a postoperative study visit to assess anomalous results in the postoperative period. Pachymetry should take place after manifest refraction has been done to avoid disturbing the cornea. 6. Preoperative and 6 Months ECD measurements will be done at three or four clinical sites by specular microscopy. 7. Pupil size should be assessed under mesopic conditions at the preoperative study visit and at months 3, 6 and 9 as well as Unscheduled Visits 8. UCNVA, UCDVA and BSCVA measurements are to be taken under photopic conditions (approximately 85 cd/m2) for each eye monocularly. 9. If the visual acuity with spectacle correction is ≥ 2 lines (10 letters) below that obtained at Visit 1, a rigid contact lens over refraction should be performed to estimate the best possible corrected visual acuity. 10. BSCVA to be completed OD and OS. 11. The slit lamp examination should include a complete survey of the anterior segment and grading of findings as detailed in Appendix B. 12. Pachymetry should be assessed only at the preoperative study visit and as needed at postoperative study Visit 7 to assess anomalous results in the postoperative period. Pachymetry should take place after manifest refraction has been done in order to avoid disturbing the cornea. 13. IOP should preferably be obtained using Goldmann applanation tonometry. 14. Dilated fundus examination (only required if loss of BSCVA occurs compared to preoperative BSCVA). Adverse events and complications were recorded at all visits from V2 onwards. The key timepoints are shown below in the tables summarizing safety and effectiveness. ### 3. Clinical Endpoints With regard to safety, no clinical endpoint with regard to safety was defined for the study, but safety assessments were included. The following safety summaries were provided for primary safety analysis with descriptive statistics by visit for all treated eyes, eyes treated for spherical myopia, and eyes treated for astigmatic myopia unless otherwise specified: - Eyes with BSCVA worse than 20/40 among eyes that had a BSCVA of 20/20 or better before surgery at each postoperative study visit - Loss of BSCVA of 1, 2, ≥ 2, and > 2 lines compared to preoperative BSCVA, with 95% CIs around the proportions - Percentage of eyes that had an increase of manifest refractive astigmatism > 2.00 D compared to the preoperative refraction, stratified by preoperative MRSE, and severity of preoperative myopia. A 95% CI around the percentage of all eyes that had an increase of > 2.00 D was displayed - Incidence of Adverse Events (AEs) by event type - Incidence of Complications - Endothelial cell density changes (subgroup analysis) - Contrast sensitivity changes under mesopic conditions - Subject symptoms and results of prespecified question domains from PROWL questionnaires With regard to effectiveness, the primary effectiveness endpoints at the time of refractive stability were provided as follows: - The percentage of eyes that achieved predictability of MRSE within ± 0.50 D - The percentage of eyes that achieved predictability of MRSE within ± 1.00 D PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 12/65 {12} - The percentage of eyes targeted for emmetropia that achieved a UCDVA of 20/40 or better (logMAR of 0.3 or better) 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. - 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. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 13/65 {13} With regard to success/failure criteria, the individual patient success included demonstration of: - Reduction of manifest spherical equivalent - Improvement of uncorrected visual acuity The study was defined as statistically successful if all primary effectiveness endpoints described above were analyzed successfully using data collected at the visit when refractive stability was achieved. Achievement of refractive stability for the study cohort required a minimum of 95% of treated eyes to have a change of ≤ 1.00 D of manifest refraction spherical equivalent between two refractions performed at least 3 months apart. The hypotheses for the endpoints (i.e., protocol-defined effectiveness success criteria) were: - Percentage of eyes that achieve predictability of MRSE within ± 0.50 D at the time of refractive stability The null hypothesis (H0) is that the proportion of eyes that achieve predictability within ± 0.50 D (π) is less than or equal to 0.80 (80%) at the time of refractive stability. The alternative hypothesis (H1) is that the proportion is greater than 0.80 (80%). $$H_0: \pi \le 0.80$$ $$H_1: \pi > 0.80$$ - Percentage of eyes that achieve predictability of MRSE within ± 1.00 D at the time of refractive stability The null hypothesis (H0) is that the proportion of eyes that achieve predictability within ± 1.00 D (π) is less than or equal to 0.90 (90%) at the time of refractive stability. The alternative hypothesis (H1) is that the proportion is greater than 0.90 (90%). $$H_0: \pi \le 0.90$$ $$H_1: \pi > 0.90$$ - Percentage of eyes targeted for emmetropia that achieve UDVA of 20/40 or better at the time of refractive stability The null hypothesis (H0) is that the proportion of eyes targeted for emmetropia and that achieve UDVA of 20/40 or better at the time of refractive stability (π), is less than or equal to 0.88 (88%). The alternative hypothesis (H1) is that the proportion is greater than 0.88 (88%). $$H_0: \pi \le 0.88$$ $$H_1: \pi > 0.88$$ ### B. Accountability of PMA Cohort At the time of database lock, of 333 eyes of 168 patients enrolled in the PMA study, 94.9% (316/333) eyes are available for analysis at the completion of the study, the 9 month post-operative visit. Table 2 presents the subject accountability: PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 14/65 {14} **Table 2: Subject Accountability** | | Preoperative n/N (%) | Operative n/N (%) | Day 1 n/N (%) | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | All treated eyes, | | | | | | | | | | Available for analysis | 333/333 (100.0%) | 333/333 (100.0%) | 333/333 (100.0%) | 333/333 (100.0%) | 325/333 (97.6%) | 315/333 (94.6%) | 313/333 (94.0%) | 316/333 (94.9%) | | Ongoing | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | | Discontinued^{a} | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 2/333 (0.6%) | 12/333 (3.6%) | 17/333 (5.1%) | | Lost to follow-up^{a} | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 2/333 (0.6%) | 10/333 (3.0%) | 12/333 (3.6%) | | Missed visit | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 8/333 (2.4%) | 16/333 (4.8%) | 8/333 (2.4%) | 0/333 (0.0%) | | % Accountability^{b} | 333/333 (100.0%) | 333/333 (100.0%) | 333/333 (100.0%) | 333/333 (100.0%) | 325/333 (97.6%) | 313/331 (95.2%) | 313/321 (97.5%) | 316/316 (100.0%) | | Eyes treated for spherical myopia, | | | | | | | | | | Available for analysis | 51/51 (100.0%) | 51/51 (100.0%) | 51/51 (100.0%) | 51/51 (100.0%) | 49/51 (96.1%) | 49/51 (96.1%) | 51/51 (100.0%) | 51/51 (100.0%) | | Ongoing | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | | Discontinued^{a} | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | | Lost to follow-up^{a} | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | | Missed visit | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 0/51 (0.0%) | 2/51 (3.9%) | 2/51 (3.9%) | 0/51 (0.0%) | 0/51 (0.0%) | | % Accountability^{b} | 51/51 (100.0%) | 51/51 (100.0%) | 51/51 (100.0%) | 51/51 (100.0%) | 49/51 (96.1%) | 49/51 (96.1%) | 51/51 (100.0%) | 51/51 (100.0%) | | Eyes treated for astigmatic myopia, | | | | | | | | | | Available for analysis | 282/282 (100.0%) | 282/282 (100.0%) | 282/282 (100.0%) | 282/282 (100.0%) | 276/282 (97.9%) | 266/282 (94.3%) | 262/282 (92.9%) | 265/282 (94.0%) | | Ongoing | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | | Discontinued^{a} | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 2/282 (0.7%) | 12/282 (4.3%) | 17/282 (6.0%) | | Lost to follow-up^{a} | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 2/282 (0.7%) | 10/282 (3.5%) | 12/282 (4.3%) | | Missed visit | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 0/282 (0.0%) | 6/282 (2.1%) | 14/282 (5.0%) | 8/282 (2.8%) | 0/282 (0.0%) | | % Accountability^{b} | 282/282 (100.0%) | 282/282 (100.0%) | 282/282 (100.0%) | 282/282 (100.0%) | 276/282 (97.9%) | 266/280 (95.0%) | 262/270 (97.0%) | 265/265 (100.0%) | Note: N is the number of eyes in the respective population, which is used as a denominator in the percentage calculations other than % accountability. a Cumulative totals are presented. For example, if an eye is discontinued at a visit, that eye is counted as discontinued at all subsequent visits. b % Accountability = [(# Available for Analysis)/(N - # Discontinued - # Ongoing] * 100. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 15/65 {15} ### C. Study Population Demographics and Baseline Parameters The demographics of the study population are typical for a refractive study performed in the US. Overall, the mean age of subjects was 32.5 years, and a majority of subjects were white (83.3%; 140/168) and female (60.1%; 101/168; Table 3). All but 3 subjects had both eyes treated in the study. Table 3 presents the demographics of the study population: **Table 3: Demographics** | | All Treated Subjects (N=168) | | --- | --- | | Age, years | | | n | 168 | | Mean (SD) | 32.5 (6.63) | | Median | 31.5 | | Min, Max | 22, 50 | | Sex, n/N (%) | | | Male | 67/168 (39.9%) | | Female | 101/168 (60.1%) | | Childbearing potential^{a} | 93/101 (92.1%) | | Ethnicity, n/N (%) | | | Hispanic or Latino | 19/168 (11.3%) | | Not Hispanic or Latino | 149/168 (88.7%) | | Race, n/N (%) | | | American Indian or Alaska Native | 1/168 (0.6%) | | Asian | 18/168 (10.7%) | | Black/African American | 3/168 (1.8%) | | Native Hawaiian or Other Pacific Islander | 0/168 (0.0%) | | White | 140/168 (83.3%) | | Other | 0/168 (0.0%) | | Multi-racial | 3/168 (1.8%) | | Unknown | 3/168 (1.8%) | | Study eye, n/N (%) | | | Right | 1/168 (0.6%) | | Left | 2/168 (1.2%) | | Both | 165/168 (98.2%) | Abbreviations: Max = maximum, Min = minimum, SD = standard deviation. Note: N is the number of subjects in the respective population, which is used as a denominator in the percentage calculation. $^{a}$ Percentage is based on female subjects. Among all treated eyes, preoperative sphere was distributed similarly across all dioptic bins (Table 4). The same was similar for the 2 subgroups, although 43% (22/51) of eyes treated for spherical myopia had sphere between -3.00 D and -5.00 D. Of the eyes treated for astigmatic myopia, nearly two-thirds (65.2%; 184/282) had preoperative cylinder between -0.25 D and -1.00 D. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 16/65 {16} **Table 4: Preoperative Manifest Refraction Parameters (All Treated Eyes)** | | All Treated Eyes (N=333) n/N (%) | Eyes Treated for Spherical Myopia (N=51) n/N (%) | Eyes Treated for Astigmatic Myopia (N=282) n/N (%) | | --- | --- | --- | --- | | Sphere | | | | | -1.00 to -2.00 D | 49/333 (14.7%) | 5/51 (9.8%) | 44/282 (15.6%) | | -2.01 to -3.00 D | 34/333 (10.2%) | 2/51 (3.9%) | 32/282 (11.3%) | | -3.01 to -4.00 D | 40/333 (12.0%) | 11/51 (21.6%) | 29/282 (10.3%) | | -4.01 to -5.00 D | 43/333 (12.9%) | 11/51 (21.6%) | 32/282 (11.3%) | | -5.01 to -6.00 D | 35/333 (10.5%) | 3/51 (5.9%) | 32/282 (11.3%) | | -6.01 to -7.00 D | 39/333 (11.7%) | 6/51 (11.8%) | 33/282 (11.7%) | | -7.01 to -8.00 D | 43/333 (12.9%) | 7/51 (13.7%) | 36/282 (12.8%) | | -8.01 to -9.00 D | 26/333 (7.8%) | 3/51 (5.9%) | 23/282 (8.2%) | | -9.01 to -10.00 D | 24/333 (7.2%) | 3/51 (5.9%) | 21/282 (7.4%) | | Cylinder (in minus notation) | | | | | 0 D | 51/333 (15.3%) | 51/51 (100.0%) | 0/282 (0.0%) | | -0.25 to -0.50 D | 107/333 (32.1%) | 0/51 (0.0%) | 107/282 (37.9%) | | -0.51 to -1.00 D | 77/333 (23.1%) | 0/51 (0.0%) | 77/282 (27.3%) | | -1.01 to -2.00 D | 74/333 (22.2%) | 0/51 (0.0%) | 74/282 (26.2%) | | -2.01 to -3.00 D | 24/333 (7.2%) | 0/51 (0.0%) | 24/282 (8.5%) | Abbreviation: D = diopter. Note: N is the number of eyes in the respective population, which is used as a denominator in the percentage calculation. ## **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. ### **1. Safety Results** The analysis of safety was based on the total cohort of 333 eyes of 168 patients available up to the 9 month post-operative visit evaluation. The safety summaries for this study are presented below in Table 5 to Table 11 and further in Table 14 to Table 16. Adverse effects and complications are reported in Table 12 to Table 13. #### **a. Eyes with best spectacle corrected visual acuity (BSCVA) worse than 20/40 (among eyes that had BSCVA 20/20 or better before surgery), at each postoperative study visit** Among all treated eyes with baseline BSCVA of 20/20 or better, none had BSCVA worse than 20/40 at the Month 3 Visit (Table 5). The same is true when all treated eyes with baseline BSCVA of 20/20 or better are divided into eyes treated for spherical myopia (Table 6) and eyes treated for astigmatic myopia (Table 7). PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 17/65 {17} Table 5: Percentage of Eyes With BSCVA Worse Than 20/40 by Visit (All Treated Eyes With Baseline BSCVA of 20/20 or Better) | BSCVA | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | | --- | --- | --- | --- | --- | --- | Worse than 20/40 0/301 (0.0%) 0/283 (0.0%) 0/275 (0.0%) 0/269 (0.0%) 0/284 (0.0%) Abbreviations: BSCVA = best spectacle-corrected distance visual acuity; Note: N is the number of eyes with preoperative BSCVA of 20/20 or better and non-missing postoperative BSCVA in each category/subcategory at a given visit, which is used as a denominator in the percentage calculation. Table 6: Percentage of Eyes With BSCVA Worse Than 20/40 by Visit (Eyes Treated for Spherical Myopia With Baseline BSCVA of 20/20 or Better) | BSCVA | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | | --- | --- | --- | --- | --- | --- | Worse than 20/40 0/43 (0.0%) 0/40 (0.0%) 0/42 (0.0%) 0/41 (0.0%) 0/43 (0.0%) Abbreviations: BSCVA = best spectacle-corrected distance visual acuity; Note: N is the number of eyes with preoperative BSCVA of 20/20 or better and non-missing postoperative BSCVA in each category/subcategory at a given visit, which is used as a denominator in the percentage calculation. Table 7: Percentage of Eyes With BSCVA Worse Than 20/40 by Visit (Eyes Treated for Astigmatic Myopia With Baseline BSCVA of 20/20 or Better) | BSCVA | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | | --- | --- | --- | --- | --- | --- | Worse than 20/40 0/258 (0.0%) 0/243 (0.0%) 0/233 (0.0%) 0/228 (0.0%) 0/241 (0.0%) Abbreviations: BSCVA = best spectacle-corrected distance visual acuity; Note: N is the number of eyes with preoperative BSCVA of 20/20 or better and non-missing postoperative BSCVA in each category/subcategory at a given visit, which is used as a denominator in the percentage calculation. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 18/65 {18} # **b. Loss of BSCVA of 1, 2, ≥ 2, and > 2 lines, compared to preoperative BSCVA** Among all treated eyes at the Month 3 Visit, none lost 2 or more lines of BSCVA from baseline, 5 eyes (1.6%; 5/305) lost 1 line from baseline. A total of 189 eyes (62.0%; 189/305) had no change in BSCVA from baseline at the Month 3 Visit (Table 8). **Table 8: Changes in Lines of BSCVA From Baseline to Each Postoperative Visit (All Treated Eyes)** | BSCVA Change | Week 1 | Month 1 | Month 3 | Month 6 | Month 9 | | --- | --- | --- | --- | --- | --- | | Loss of ≥ 2 lines | | | | | | | Eyes, n/N (%) | 4/333 (1.2%) | 0/313 (0.0%) | 0/305 (0.0%) | 0/299 (0.0%) | 0/316 (0.0%) | | 95% CI | (0.0, 2.4) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | | Loss of > 2 lines | | | | | | | Eyes, n/N (%) | 0/333 (0.0%) | 0/313 (0.0%) | 0/305 (0.0%) | 0/299 (0.0%) | 0/316 (0.0%) | | 95% CI | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | | Loss of 2 lines | | | | | | | Eyes, n/N (%) | 4/333 (1.2%) | 0/313 (0.0%) | 0/305 (0.0%) | 0/299 (0.0%) | 0/316 (0.0%) | | 95% CI | (0.0, 2.4) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | | Loss of 1 line | | | | | | | Eyes, n/N (%) | 20/333 (6.0%) | 10/313 (3.2%) | 5/305 (1.6%) | 2/299 (0.7%) | 4/316 (1.3%) | | 95% CI | (3.5, 8.6) | (1.2, 5.1) | (0.2, 3.1) | (0.0, 1.6) | (0.0, 2.5) | | No change | | | | | | | Eyes, n/N (%) | 245/333 (73.6%) | 210/313 (67.1%) | 189/305 (62.0%) | 198/299 (66.2%) | 202/316 (63.9%) | | 95% CI | (68.8, 78.3) | (61.9, 72.3) | (56.5, 67.4) | (60.9, 71.6) | (58.6, 69.2) | | Gain of 1 line | | | | | | | Eyes, n/N (%) | 54/333 (16.2%) | 83/313 (26.5%) | 101/305 (33.1%) | 88/299 (29.4%) | 96/316 (30.4%) | | 95% CI | (12.3, 20.2) | (21.6, 31.4) | (27.8, 38.4) | (24.3, 34.6) | (25.3, 35.5) | | Gain of ≥ 2 lines | | | | | | | Eyes, n/N (%) | 10/333 (3.0%) | 10/313 (3.2%) | 10/305 (3.3%) | 11/299 (3.7%) | 14/316 (4.4%) | | 95% CI | (1.2, 4.8) | (1.2, 5.1) | (1.3, 5.3) | (1.5, 5.8) | (2.2, 6.7) | Abbreviations: BSCVA = best spectacle-corrected distance visual acuity; CI = confidence interval. Note: Change is calculated as the difference between postoperative BSCVA result minus preoperative BSCVA result. N is the number of eyes with non-missing preoperative and postoperative results in each category/subcategory at a given visit, which is used as a denominator in the percentage calculation. # **c. Percentage of eyes that had an increase of manifest refractive astigmatism > 2.00 D compared to the preoperative refraction** Among all treated eyes, none had an increase of manifest refractive astigmatism greater than 2.00D at the Month 3 Visit (Table 9). The same is true when all treated eyes are divided into eyes treated for spherical myopia (Table 10) and eyes treated for astigmatic myopia (Table 11). PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 19/65 {19} Table 9: Percentage of Eyes With Increase of Manifest Refractive Astigmatism by Visit (All Treated Eyes) | ≤ -2 D change from baseline in cylinder | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | | --- | --- | --- | --- | --- | --- | | Eyes, n/N (%) | 0/333 (0.0%) | 0/313 (0.0%) | 0/305 (0.0%) | 0/299 (0.0%) | 0/316 (0.0%) | | 95% CI | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | Abbreviations: CI = confidence interval; D = diopter. Note: N is the number of eyes with non-missing preoperative and postoperative results in each category/subcategory at a given visit, which is used as a denominator in the percentage calculation. Table 10: Percentage of Eyes With Increase of Manifest Refractive Astigmatism by Visit (Eyes Treated for Spherical Myopia) | ≤ -2 D change from baseline in cylinder | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | | --- | --- | --- | --- | --- | --- | | Eyes, n (%) | 0/51 (0.0%) | 0/47 (0.0%) | 0/48 (0.0%) | 0/49 (0.0%) | 0/51 (0.0%) | | 95% CI | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | Abbreviations: CI = confidence interval; D = diopter. Note: N is the number of eyes with non-missing preoperative and postoperative results in each category/subcategory at a given visit, which is used as a denominator in the percentage calculation. Table 11: Percentage of Eyes With Increase of Manifest Refractive Astigmatism by Visit (Eyes Treated for Astigmatic Myopia) | ≤ -2 D change from baseline in cylinder | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | | --- | --- | --- | --- | --- | --- | | Eyes, n (%) | 0/282 (0.0%) | 0/266 (0.0%) | 0/257 (0.0%) | 0/250 (0.0%) | 0/265 (0.0%) | | 95% CI | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | Abbreviations: CI = confidence interval; D = diopter. Note: N is the number of eyes with non-missing preoperative and postoperative results in each category/subcategory at a given visit, which is used as a denominator in the percentage calculation. ### d. Adverse Events and Complications that occurred in the PMA clinical study: #### Adverse Events: - The most frequently reported AE throughout the study was **BSCVA worse than 20/25**, if 20/20 or better preoperatively, occurring in 5 eyes (1.5%; 5/333); Table 12). None of these events were serious or led to treatment discontinuation (all 5 resolved within 90 days; 3 resolved within 3 weeks). - Two eyes experienced **loss of > 2 lines BSCVA** at 1 week (1 resolved by 1 month and 1 resolved by 3 months). - One eye was reported at 1 week to have BSCVA worse than 20/25, if 20/20 or better preoperatively, associated with corneal edema (visual acuity improved by 1 month, the **corneal edema** (at 1 month or later) resolved by 6 months). - One eye experienced a **miscreated flap** and was converted to PRK (reported as both a device deficiency and a protocol deviation). - At the Month 3 Visit, 2 AEs were reported in the same eye: 1 **corneal edema at 1 month** PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 20/65 {20} or later and 1 BSCVA worse than 20/25 (in an eye that had preoperative BSCVA 20/20 or better). Both AEs were due to trauma not related to the study device or the study procedure. The corneal edema resolved within 4 days and the BSCVA worse than 20/25 resolved by the Month 6 visit. - Two eyes of 1 subject were noted to have corneal pigmentation (i.e., Krukenberg spindles) at the 1 day visit. This was considered unrelated to the device or the procedure. - One eye developed a retinal vein occlusion observed at the 1 week visit. This was considered unrelated to the device or the procedure. Complications: - The most frequently reported complication or potential AE throughout the study was SPK, occurring in 128 eyes (38.4% (128/333); Table 13). - At the Month 3 Visit, complications or potential AEs reported were SPK (2.4%; 8/331), other: conjunctival hyperaemia (0.9%; 3/331), subconjunctival hemorrhage (0.6%; 2/331), trace microstriae (0.6%), debris in the interface (0.6%; 2/331), vitreous floaters (0.6%; 2/331), allergic conjunctivitis (0.6%; 2/331), corneal haze (0.6%; 2/331), double/ghost images in operative eye (0.3%; 1/331), iritis (0.3%; 1/331), other: face injury (0.3%; 1/331), and peripheral corneal epithelial defect at 1 month or later (0.3%; 1/331). - One eye underwent corneal flap lifting between 1 day to 1 month post-surgery for a wrinkled flap considered related to eye rubbing; this eye maintained 20/20 or better BSCVA throughout the course of the study. - One eye had corneal haze starting at Month 3 that was ongoing at study completion. This eye was followed up with resolution of corneal haze at 21 months postoperative. There were no deaths, serious adverse events (SAEs), or other significant AEs during the study. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 21/65 {21} **Table 12: Incidence of Adverse Events by Visit (All Treated Eyes)** | AEs | Operative n/N (%) | Day 1 n/N (%) | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | Total n/N (%) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | BSCVA worse than 20/25, if 20/20 or better preoperatively | 0/333 (0.0%) | 0/333 (0.0%) | 4/333 (1.2%) | 0/333 (0.0%) | 1/331 (0.3%) | 0/321 (0.0%) | 0/316 (0.0%) | 5/333 (1.5%) | | Corneal edema at 1 month or later | 0/333 (0.0%) | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 1/331 (0.3%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Loss of > 2 lines (10 letters) | 0/333 (0.0%) | 0/333 (0.0%) | 2/333 (0.6%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | BSCVA | | | | | | | | | | Other ocular event: Corneal pigmentation | 0/333 (0.0%) | 2/333 (0.6%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Miscreated flap (lost, incomplete, too thin) | 1/333 (0.3%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Other ocular event: Retinal vein occlusion | 0/333 (0.0%) | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | Abbreviations: AE = adverse events; BSCVA = best spectacle-corrected distance visual acuity. Note: AEs reported in the table are predetermined and not coded. AEs that start on or after the visit and before the next visit are counted under the first visit. N is the number of eyes from subjects who are active in the trial at a given visit, which is used as a denominator in the percentage calculation. The N for the Total column is the total number of treated eyes. The counts under the Total column are the unique numbers of eyes having the event and therefore may not be equal to the sum of counts in the visit columns. **Table 13: Incidence of Complications/Possible Adverse Events by Visit (All Treated Eyes)** | Complications | Operative n/N (%) | Day 1 n/N (%) | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | Total n/N (%) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Superficial punctate keratopathy (SPK) | 0/333 (0.0%) | 63/333 (18.9%) | 36/333 (10.8%) | 29/333 (8.7%) | 8/331 (2.4%) | 9/321 (2.8%) | 10/316 (3.2%) | 128/333 (38.4%) | | Subconjunctival hemorrhage | 0/333 (0.0%) | 66/333 (19.8%) | 0/333 (0.0%) | 0/333 (0.0%) | 2/331 (0.6%) | 1/321 (0.3%) | 0/316 (0.0%) | 68/333 (20.4%) | | Trace microstriae | 0/333 (0.0%) | 11/333 (3.3%) | 5/333 (1.5%) | 6/333 (1.8%) | 2/331 (0.6%) | 0/321 (0.0%) | 0/316 (0.0%) | 24/333 (7.2%) | | Diffuse lamellar keratitis (Grade 2 or less) | 0/333 (0.0%) | 16/333 (4.8%) | 5/333 (1.5%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 20/333 (6.0%) | | Debris in the interface | 1/333 (0.3%) | 9/333 (2.7%) | 3/333 (0.9%) | 2/333 (0.6%) | 2/331 (0.6%) | 2/321 (0.6%) | 0/316 (0.0%) | 18/333 (5.4%) | | Corneal edema between 1 week to less than 1 month after procedure | 0/333 (0.0%) | 5/333 (1.5%) | 5/333 (1.5%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 10/333 (3.0%) | | Meibomian gland dysfunction | 0/333 (0.0%) | 0/333 (0.0%) | 4/333 (1.2%) | 1/333 (0.3%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 5/333 (1.5%) | | Other: Conjunctival hyperaemia | 0/333 (0.0%) | 1/333 (0.3%) | 1/333 (0.3%) | 0/333 (0.0%) | 3/331 (0.9%) | 0/321 (0.0%) | 0/316 (0.0%) | 5/333 (1.5%) | | Vitreous floaters | 0/333 (0.0%) | 1/333 (0.3%) | 2/333 (0.6%) | 0/333 (0.0%) | 2/331 (0.6%) | 0/321 (0.0%) | 0/316 (0.0%) | 5/333 (1.5%) | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 22/65 {22} **Table 13: Incidence of Complications/Possible Adverse Events by Visit (All Treated Eyes)** | Complications | Operative n/N (%) | Day 1 n/N (%) | Week 1 n/N (%) | Month 1 n/N (%) | Month 3 n/N (%) | Month 6 n/N (%) | Month 9 n/N (%) | Total n/N (%) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Allergic conjunctivitis | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 2/331 (0.6%) | 0/321 (0.0%) | 2/316 (0.6%) | 4/333 (1.2%) | | Corneal abrasion | 0/333 (0.0%) | 4/333 (1.2%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 4/333 (1.2%) | | Corneal haze | 0/333 (0.0%) | 0/333 (0.0%) | 2/333 (0.6%) | 0/333 (0.0%) | 2/331 (0.6%) | 0/321 (0.0%) | 0/316 (0.0%) | 4/333 (1.2%) | | Loose epithelium | 1/333 (0.3%) | 3/333 (0.9%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 4/333 (1.2%) | | Epithelium in the interface | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 1/333 (0.3%) | 0/331 (0.0%) | 1/321 (0.3%) | 1/316 (0.3%) | 3/333 (0.9%) | | Rough epithelium | 0/333 (0.0%) | 2/333 (0.6%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 3/333 (0.9%) | | Conjunctivitis | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 2/321 (0.6%) | 0/316 (0.0%) | 2/333 (0.6%) | | Corneal flap lifting between 1 day to 1 month post-surgery for wrinkled flap | 0/333 (0.0%) | 1/333 (0.3%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Dry eye | 0/333 (0.0%) | 0/333 (0.0%) | 2/333 (0.6%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Epithelium at the flap edge | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 1/333 (0.3%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Other: Conjunctivitis viral | 0/333 (0.0%) | 0/333 (0.0%) | 2/333 (0.6%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Other: Corneal oedema | 0/333 (0.0%) | 1/333 (0.3%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Other: Hordeolum | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 1/333 (0.3%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Steroid-induced IOP increase | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 2/333 (0.6%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 2/333 (0.6%) | | Blepharitis | 0/333 (0.0%) | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Double/ghost images in operative eye | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 1/331 (0.3%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Iritis | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 1/331 (0.3%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Mucus under edge of flap | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 1/333 (0.3%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Other: Corneal disorder | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Other: Corneal epithelium defect | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Other: Corneal erosion | 0/333 (0.0%) | 1/333 (0.3%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Other: Eye injury | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/331 (0.0%) | 1/321 (0.3%) | 0/316 (0.0%) | 1/333 (0.3%) | | Other: Face injury | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 1/331 (0.3%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | | Peripheral corneal epithelial defect at 1 month or later | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 0/333 (0.0%) | 1/331 (0.3%) | 0/321 (0.0%) | 0/316 (0.0%) | 1/333 (0.3%) | Abbreviations: AE = adverse events; IOP = intraocular pressure. Note: Complications reported in the table are predetermined and not coded. Complications that start on or after a visit and before the next visit are counted under the first visit. n is the number of eyes from subjects who are active in the trial at a given visit, which is used as a denominator in the percentage calculation. The N for the Total column is the total number of treated eyes. The counts under Total column are the unique number of eyes having the complication and therefore may not be equal to the sum of counts in the visit columns. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 23/65 {23} # e. Endothelial cell density (ECD) changes (substudy of 124 eyes) Among all treated eyes within the ECD substudy, mean endothelial density was 2803.24 cells/mm² preoperatively and 2811.76 cells/mm² at the Month 6 Visit (Table 14). Only 1 eye at the Month 6 Visit had endothelial cell loss ≥ 10%. Table 14: Endothelial Cell Density (cells/mm²) by Visit | Visit Value Statistic | All Treated Eyes | Eyes Treated for Spherical Myopia | Eyes Treated for Astigmatic Myopia | | --- | --- | --- | --- | | **Preoperative** | | | | | Actual value | | | | | n | 124 | 10 | 114 | | Mean (SD) | 2803.24 (315.569) | 2891.71 (254.174) | 2795.48 (320.153) | | Median | 2813.00 | 2784.85 | 2817.50 | | Minimum, maximum | 1867.5, 3455.2 | 2615.8, 3436.2 | 1867.5, 3455.2 | | **Month 6** | | | | | Actual value | | | | | n | 111 | 11 | 100 | | Mean (SD) | 2811.76 (297.642) | 2820.45 (251.615) | 2810.81 (303.364) | | Median | 2833.00 | 2819.70 | 2833.15 | | Minimum, maximum | 1926.0, 3382.8 | 2420.0, 3297.5 | 1926.0, 3382.8 | | Change from baseline | | | | | n | 109 | 10 | 99 | | Mean (SD) | 8.68 (134.452) | -58.44 (133.986) | 15.46 (133.294) | | Median | 10.00 | -2.65 | 11.80 | | Minimum, maximum | -353.4, 636.1 | -353.4, 109.5 | -265.7, 636.1 | | Categorical percent loss in ECD, n/N (%) | | | | | 0 | 57/109 (52.3%) | 5/10 (50.0%) | 52/99 (52.5%) | | -10 to ≤ 0 | 51/109 (46.8%) | 4/10 (40.0%) | 47/99 (47.5%) | | -20 to ≤ -10 | 1/109 (0.9%) | 1/10 (10.0%) | 0/99 (0.0%) | | -30 to ≤ -20 | 0/109 (0.0%) | 0/10 (0.0%) | 0/99 (0.0%) | | -40 to ≤ -30 | 0/109 (0.0%) | 0/10 (0.0%) | 0/99 (0.0%) | | -50 to ≤ -40 | 0/109 (0.0%) | 0/10 (0.0%) | 0/99 (0.0%) | | ≤ -50 | 0/109 (0.0%) | 0/10 (0.0%) | 0/99 (0.0%) | Abbreviations: ECD = endothelial cell density; SD = standard deviation. Note: Baseline is defined as the last measurement prior to LASIK surgery. Change from baseline is calculated as postoperative result minus baseline result. N is the number of eyes with non-missing preoperative and postoperative results, which is used as a denominator in the percentage calculation. Percent loss in ECD is calculated as: (Postoperative Result – Baseline Result)*100 / Baseline Result. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 24/65 {24} # **f. Contrast sensitivity changes under mesopic conditions** The change from baseline to the Month 6 Visit in contrast sensitivity among subjects participating in the contrast sensitivity substudy is presented in Table 15. Under glare conditions, the mean (SD) change in contrast sensitivity from baseline to 6 months at 1.5, 3, 6, and 12 cpd ranged from 0.06 (0.184) to 0.10 (0.198) logCS, respectively. Without glare, the mean (SD) change in contrast sensitivity from baseline to 6 months at 1.5, 3, 6, and 12 cpd ranged from 0.03 (0.159) to 0.15 (0.216) logCS, respectively. **Table 15: Contrast Sensitivity by Visit (All Treated Subjects)** | Contrast sensitivity, logCS | Preoperative | Month 6 | | --- | --- | --- | | Mean contrast sensitivity with glare at 1.5 cpd | | | | Actual value | | | | n | 47 | 41 | | Mean (SD) | 1.98 (0.237) | 2.03 (0.198) | | Median | 2.02 | 2.05 | | Min, Max | 1.2, 2.3 | 1.6, 2.4 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.06 (0.184) | | Median | | 0.05 | | Min, Max | | -0.4, 0.7 | | Mean contrast sensitivity with glare at 3 cpd | | | | Actual value | | | | n | 47 | 41 | | Mean (SD) | 2.05 (0.234) | 2.12 (0.190) | | Median | 2.10 | 2.15 | | Min, Max | 1.4, 2.4 | 1.6, 2.4 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.08 (0.208) | | Median | | 0.05 | | Min, Max | | -0.5, 0.8 | | Mean contrast sensitivity with glare at 6 cpd | | | | Actual value | | | | n | 47 | 41 | | Mean (SD) | 1.70 (0.245) | 1.83 (0.241) | | Median | 1.75 | 1.83 | | Min, Max | 1.0, 2.2 | 1.1, 2.3 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.10 (0.202) | | Median | | 0.09 | | Min, Max | | -0.2, 0.7 | Mean contrast sensitivity with glare at 12 cpd Actual value PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 25/65 {25} **Table 15: Contrast Sensitivity by Visit (All Treated Subjects)** | Contrast sensitivity, logCS | Preoperative | Month 6 | | --- | --- | --- | | n | 47 | 41 | | Mean (SD) | 1.13 (0.290) | 1.26 (0.331) | | Median | 1.14 | 1.27 | | Min, Max | 0.6, 2.0 | 0.5, 2.3 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.10 (0.198) | | Median | | 0.14 | | Min, Max | | -0.4, 0.5 | | Mean contrast sensitivity without glare at 1.5 cpd | | | | Actual value | | | | n | 47 | 41 | | Mean (SD) | 2.12 (0.188) | 2.14 (0.165) | | Median | 2.15 | 2.18 | | Min, Max | 1.4, 2.4 | 1.7, 2.4 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.03 (0.159) | | Median | | 0.03 | | Min, Max | | -0.3, 0.6 | | Mean contrast sensitivity without glare at 3 cpd | | | | Actual value | | | | n | 47 | 41 | | Mean (SD) | 2.17 (0.199) | 2.20 (0.173) | | Median | 2.25 | 2.25 | | Min, Max | 1.5, 2.4 | 1.7, 2.4 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.05 (0.163) | | Median | | 0.06 | | Min, Max | | -0.3, 0.5 | | Mean contrast sensitivity without glare at 6 cpd | | | | Actual value | | | | n | 47 | 41 | | Mean (SD) | 1.81 (0.275) | 1.91 (0.259) | | Median | 1.80 | 1.90 | | Min, Max | 1.2, 2.4 | 1.2, 2.4 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.11 (0.221) | | Median | | 0.10 | | Min, Max | | -0.3, 0.7 | | Mean contrast sensitivity without glare at 12 cpd | | | | Actual value | | | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 26/65 {26} **Table 15: Contrast Sensitivity by Visit (All Treated Subjects)** | Contrast sensitivity, logCS | Preoperative | Month 6 | | --- | --- | --- | | n | 47 | 41 | | Mean (SD) | 1.18 (0.355) | 1.34 (0.356) | | Median | 1.14 | 1.30 | | Min, Max | 0.6, 2.3 | 0.6, 2.3 | | Change from baseline | | | | n | | 38 | | Mean (SD) | | 0.15 (0.216) | | Median | | 0.13 | | Min, Max | | -0.3, 0.7 | Abbreviations: cpd = cycles per degree; LASIK = laser in situ keratomileusis; Max = maximum, Min = minimum, SD = standard deviation. Note: Baseline is defined as the last measurement prior to LASIK surgery. Change from baseline is calculated as postoperative result minus baseline result. # **g. Patient-Reported Outcomes with LASIK (PROWL) questionnaire - Subject Symptoms and results for prespecified question domains :** Among all treated subjects at the Month 3 Visit, all PROWL questionnaire (Patient-Reported Outcomes with LASIK) domains showed score improvements from baseline, with change score mean (SD) values, ranging from 1.3 (8.28) units for eye dryness, to 42.1 (34.12) units for vision satisfaction (Table 16) Mean (SD) value for satisfaction with LASIK surgery was 96.6 (6.53) units. **Table 16: Patient-Reported Outcomes With LASIK Questionnaires by Visit (All Treated Subjects)** | | Preoperative | Month 3 | Month 6 | Month 9 | | --- | --- | --- | --- | --- | | Far vision | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 85.1 (15.62) | 95.1 (8.02) | 95.7 (7.21) | 95.9 (7.26) | | Median | 90.0 | 100.0 | 100.0 | 100.0 | | Min, Max | 10, 100 | 53, 100 | 57, 100 | 60, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 9.2 (14.37) | 9.9 (14.43) | 10.2 (14.41) | | Median | | 5.0 | 6.7 | 6.7 | | Min, Max | | -25, 58 | -37, 63 | -30, 63 | | Near vision | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 89.9 (12.77) | 97.1 (6.97) | 97.7 (5.27) | 97.5 (6.86) | | Median | 93.3 | 100.0 | 100.0 | 100.0 | | Min, Max | 27, 100 | 53, 100 | 78, 100 | 53, 100 | | Change from baseline | | | | | | N | | 153 | 151 | 159 | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 27/65 {27} **Table 16: Patient-Reported Outcomes With LASIK Questionnaires by Visit (All Treated Subjects)** | | Preoperative | Month 3 | Month 6 | Month 9 | | --- | --- | --- | --- | --- | | Mean (SD) | | 6.6 (13.15) | 6.8 (12.48) | 7.1 (13.13) | | Median | | 5.0 | 0.0 | 5.0 | | Min, Max | | -35, 53 | -22, 53 | -47, 53 | | Eye dryness | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 92.2 (7.70) | 93.5 (6.64) | 94.3 (5.80) | 94.9 (6.41) | | Median | 93.8 | 93.8 | 96.9 | 96.9 | | Min, Max | 71, 100 | 68, 100 | 75, 100 | 68, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 1.3 (8.28) | 2.0 (7.87) | 2.6 (8.08) | | Median | | 0.0 | 0.0 | 1.0 | | Min, Max | | -23, 23 | -19, 26 | -22, 29 | | Symptoms – Double images | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 87.7 (14.71) | 97.7 (9.29) | 97.6 (8.84) | 98.7 (5.03) | | Median | 92.5 | 100.0 | 100.0 | 100.0 | | Min, Max | 29, 100 | 31, 100 | 42, 100 | 67, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 9.8 (16.07) | 9.3 (16.80) | 10.6 (14.52) | | Median | | 7.5 | 7.5 | 7.5 | | Min, Max | | -47, 60 | -50, 71 | -33, 71 | | Symptoms – Glare | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 82.0 (19.54) | 94.0 (13.17) | 95.4 (11.05) | 95.9 (9.72) | | Median | 89.8 | 100.0 | 100.0 | 100.0 | | Min, Max | 22, 100 | 13, 100 | 35, 100 | 48, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 12.0 (18.97) | 13.5 (21.39) | 13.2 (20.08) | | Median | | 7.5 | 8.3 | 7.5 | | Min, Max | | -40, 78 | -48, 78 | -52, 78 | | Symptoms – Halo | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 79.1 (20.59) | 88.9 (16.65) | 92.2 (13.69) | 93.7 (12.66) | | Median | 88.0 | 100.0 | 100.0 | 100.0 | | Min, Max | 18, 100 | 19, 100 | 35, 100 | 31, 100 | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 28/65 {28} **Table 16: Patient-Reported Outcomes With LASIK Questionnaires by Visit (All Treated Subjects)** | | Preoperative | Month 3 | Month 6 | Month 9 | | --- | --- | --- | --- | --- | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 9.8 (21.55) | 12.7 (22.66) | 13.6 (22.64) | | Median | | 7.5 | 10.4 | 10.0 | | Min, Max | | -38, 65 | -49, 74 | -58, 74 | | Symptoms – Starbursts | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 73.1 (23.16) | 85.7 (18.37) | 89.5 (15.52) | 89.1 (14.72) | | Median | 78.4 | 95.0 | 100.0 | 100.0 | | Min, Max | 5, 100 | 19, 100 | 23, 100 | 38, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 12.8 (26.33) | 16.7 (25.38) | 15.2 (25.90) | | Median | | 9.6 | 15.3 | 10.6 | | Min, Max | | -46, 95 | -65, 95 | -63, 95 | | Driving | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 87.1 (14.04) | 95.6 (7.36) | 96.2 (7.06) | 96.3 (7.27) | | Median | 87.5 | 100.0 | 100.0 | 100.0 | | Min, Max | 19, 100 | 60, 100 | 56, 100 | 50, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 7.8 (13.65) | 8.1 (13.22) | 8.4 (13.02) | | Median | | 6.3 | 6.3 | 6.3 | | Min, Max | | -38, 54 | -44, 60 | -31, 60 | | Vision clarity^{1} | | | | | | Actual value | | | | | | n | 168 | 153 | 150 | 159 | | Mean (SD) | 85.3 (26.58) | 87.2 (23.63) | 91.1 (21.02) | 93.7 (17.16) | | Median | 100.0 | 100.0 | 100.0 | 100.0 | | Min, Max | 17, 100 | 20, 100 | 0, 100 | 21, 100 | | Change from baseline | | | | | | n | | 153 | 150 | 159 | | Mean (SD) | | 1.5 (33.57) | 5.6 (29.97) | 7.9 (29.24) | | Median | | 0.0 | 0.0 | 0.0 | | Min, Max | | -80, 83 | -100, 83 | -79, 83 | | Vision satisfaction | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 49.2 (28.02) | 91.8 (16.15) | 92.2 (17.28) | 94.2 (12.40) | PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 29/65 {29} **Table 16: Patient-Reported Outcomes With LASIK Questionnaires by Visit (All Treated Subjects)** | | Preoperative | Month 3 | Month 6 | Month 9 | | --- | --- | --- | --- | --- | | Median | 50.0 | 100.0 | 100.0 | 100.0 | | Min, Max | 0, 100 | 0, 100 | 0, 100 | 0, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 42.1 (34.12) | 41.9 (32.77) | 45.0 (30.69) | | Median | | 40.0 | 40.0 | 40.0 | | Min, Max | | -100, 100 | -80, 100 | -40, 100 | | Vision clarity^{2} | | | | | | Actual value | | | | | | n | 168 | 153 | 151 | 159 | | Mean (SD) | 73.4 (21.44) | 88.0 (17.78) | 89.4 (17.37) | 90.8 (16.31) | | Median | 66.7 | 100.0 | 100.0 | 100.0 | | Min, Max | 0, 100 | 0, 100 | 33, 100 | 0, 100 | | Change from baseline | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 14.4 (26.43) | 14.8 (23.92) | 16.1 (23.68) | | Median | | 0.0 | 0.0 | 33.3 | | Min, Max | | -100, 67 | -33, 67 | -67, 67 | | Satisfaction with LASIK surgery | | | | | | Actual value | | | | | | n | | 153 | 151 | 159 | | Mean (SD) | | 96.6 (6.53) | 96.6 (6.99) | 96.8 (5.99) | | Median | | 100.0 | 100.0 | 100.0 | | Min, Max | | 70, 100 | 64, 100 | 61, 100 | Abbreviations: LASIK = laser in situ keratomileusis; Max = maximum, Min = minimum, SD = standard deviation Note: Baseline is defined as the last measurement prior to surgery. Change from baseline is calculated as postoperative result minus baseline result. $^{1}$Vision clarity domain includes PROWL-PRQ questions 34, 34a, 35, 35a, 36, 36a and PROWL-POQ questions 28, 28a, 29, 29a, 30, 30a. $^{2}$Vision clarity domain includes PROWL-PRQ question 5 and PROWL-POQ question 5. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 30/65 {30} ## 2. Effectiveness Results The analysis of effectiveness was based on 316 eyes up to the 9 month time point. Key effectiveness outcomes are presented in Table 17 to Table 22. Additional effectiveness variables are presented in Table 23 to Table 46. ### a. Primary Effectiveness Endpoints: Percentage of Eyes With Predictability of MRSE within $\pm 0.50$ D and MRSE within $\pm 1.00$ D of intended MRSE Among all treated eyes at the Month 3 Visit, 94.0% (313.02/333) had MRSE within $\pm 0.50$ D of predicted MRSE and 99.1% (330.00/333) had MRSE within $\pm 1.00$ D of predicted MRSE (Table 17). Similar results at the Month 3 Visit were observed in the 2 subsets, treated for spherical myopia and for myopic astigmatism. Sensitivity analyses using all treated eyes with observed case data were similar to the primary Analysis. The first primary endpoint, percentage of eyes with MRSE within $\pm 0.50$ D of predicted MRSE, showed that 94.0% (313.02/333) of all treated eyes had predictable MRSE within $\pm 0.50$ D. Because the lower confidence limit of 91.3% is greater than the 80% threshold for the percentage of eyes with predictable MRSE within $\pm 0.50$ D, the pre-specified performance standard was exceeded. Similarly, the second primary endpoint, percentage of eyes with MRSE within $\pm 1.00$ D of predicted MRSE, showed that 99.1% (330.00/333) of all treated eyes had predictable MRSE within $\pm 1.00$ D. Because the lower confidence limit of 98.1% is greater than the 90% threshold for the percentage of eyes with predictable MRSE within $\pm 1.00$ D, the pre-specified performance standard was exceeded. **Table 17: Percentage of Eyes With Predictability of MRSE (All Treated Eyes With Multiple Imputations)** | Predictability of MRSE, % | Week 1 | Month 1 | Month 3 | Month 6 | Month 9 | | --- | --- | --- | --- | --- | --- | | **$\pm 0.50$ D** | | | | | | | Percentage of eyes % (n/N) | 95.5% (318.02/333) | 93.6% (311.69/333) | 94.0% (313.02/333) | 91.8% (305.69/333) | 92.5% (308.03/333) | | p-value | <0.0001* | <0.0001 | <0.0001 | <0.0001 | <0.0001 | | 95% CI | 93.3, 97.7* | 90.9, 96.3 | 91.3, 96.7 | 88.6, 94.9 | 89.5, 95.4 | | **$\pm 1.00$ D** | | | | | | | Percentage of eyes % (n/N) | 98.8% (329.00/333) | 98.7% (328.67/333) | 99.1% (330.00/333) | 98.5% (328.01/333) | 99.1% (330.00/333) | | p-value | <0.0001* | <0.0001 | <0.0001* | <0.0001* | <0.0001 | | 95% CI | 97.6, 100.0* | 97.5, 100.0 | 98.1, 100.0* | 97.2, 99.8* | 98.1, 100.0 | Abbreviations: CI = confidence interval; D = diopter; MRSE = manifest refraction spherical equivalent, n = numerator; N = denominator; % = percentage (n/N) Note: Predictability of MRSE is calculated as the absolute difference between postoperative MRSE and targeted MRSE. If targeted MRSE is emmetropic, then it is equal to postoperative MRSE. 95% CIs and p-values are based on normal approximation for binomial proportion. Numerators (n) are calculated as the product of the percentage and the denominator rounded to the nearest 0.01. CIs and p-values are calculated from a single imputation when there is zero variance among multiple imputations. PMA P990027/S021: FDA Summary of Safety and Effectiveness Page 31/65 {31} **Table 18: Percentage of Eyes With Predictability of MRSE (Eyes Treated for Spherical Myopia With Multiple Imputations)** | Predictability of MRSE, % | Week 1 | Month 1 | Month 3 | Month 6 | Month 9 | | --- | --- | --- | --- | --- | --- | | ± 0.50 D | | | | | | | Percentage of eyes% | 98.0% | 92.8% | 94.0% | 93.8% | 96.1% | | (n/N) | (49.98/51) | (47.33/51) | (47.94/51) | (47.84/51) | (49.01/51) | | 95% CI | 94.2, 100.0* | 85.2, 100.0 | 87.5, 100.0 | 87.1, 100.0 | 90.8, 100.0* | | ± 1.00 D | | | | | | | Percentage of eyes | 100.0% | 100.0% | 100.0% | 98.0% | 100.0% | | %(n/N) | (51/51) | (51/51) | (51/51) | (49.98/51) | (51/51) | | 95% CI | 100.0, 100.0* | 100…