ALLEGRETTO WAVE EYE-Q EXCIMER LASER SYSTEM

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION | Device Generic Name: | Ophthalmic Excimer Laser | | --- | --- | | Device Trade Name: System | ALLEGRETTO WAVE® Eye-Q Excimer Laser | | Device Procode: | LZS | | Applicant's Name and Address: | Alcon Research, Ltd. 6201 South Freeway Fort Worth, Texas 76134 USA Telephone: (817)-551-8651 | | Date of Panel Recommendation: | None | | Premarket Approval Application (PMA) Number: | P020050/S12 | | Date of FDA Notice of Approval | September 27, 2013 | The original PMA (P020050) was approved October 7, 2003, and the ALLEGRETTO WAVE® Eye-Q Excimer Laser System is indicated for performing Laser Assisted *in situ* Keratomileusis (LASIK) treatments in patients 18 years of age or older for the reduction or elimination of myopic refractive errors up to -12.0 diopters (D) of sphere with and without astigmatic refractive errors up to 6.0 D; and in patients with documented evidence of a stable manifest refraction defined as $\leq 0.50$ D of preoperative spherical equivalent shift over one year prior to surgery. The Safety and Effectiveness Data (SSED) to support the indication is available on the CDRH website and is incorporated by reference here: http://www.accessdata.fda.gov/cdrh_docs/pdf2/P020050b.pdf. A Panel-Track Supplement to the original PMA (P020050/S4) was approved July 26, 2006, and expanded the indications for use of the ALLEGRETTO WAVE® Eye-Q Excimer Laser System for performing wavefront-guided LASIK treatments for the reduction or elimination of up to -7.00 diopters (D) of spherical equivalent myopia or myopia with astigmatism, with up to -7.00 D of spherical component and up to 3.00 D of astigmatic component at the spectacle plane surgery in patients 18 years of age or older with documentation of a stable manifest refraction defined as $\leq 0.50$ D of preoperative spherical equivalent shift over one year prior to surgery. The SSED to support the indication is available on the CDRH website and is incorporated by reference here: http://www.accessdata.fda.gov/cdrh_docs/pdf2/P020050S004a.pdf. PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 1 of 39 {1} ## II. INDICATIONS FOR USE The WaveLight ALLEGRETTO WAVE® Eye-Q Excimer Laser System used in conjunction with the WaveLight ALLEGRO Topolyzer (topographer) and T-CAT treatment planning software is indicated for performing topography-guided laser assisted in situ keratomileusis (T-CAT LASIK): - for the reduction or elimination of up to -9.00 diopters (D) of spherical equivalent myopia or myopia with astigmatism, with up to -8.00 D of spherical component and up to -3.00 D of astigmatic component at the spectacle plane; - in patients who are 18 years of age or older; and, - in patients with documentation of a stable manifest refraction defined as 0.50 D or less of preoperative spherical equivalent shift over one year prior to surgery. ### III. CONTRAINDICATIONS T-CAT LASIK treatments are contraindicated in: - Pregnant or nursing women - Patients with a weakened immune system, including diagnosed collagen vascular, autoimmune or immunodeficiency disease - Patients with degenerations of structure of the cornea, including diagnosed keratoconus or any clinical pictures suggestive to keratoconus - Patients with severe dry eye - Patients with eyes that have a calculated residual stromal bed thickness that is less than 250 microns - Patients with a recurrent corneal erosion - Patients with advanced glaucoma - Patients with uncontrolled diabetes ### IV. WARNINGS AND PRECAUTION The warnings and precautions can be found in the ALLEGRETTO WAVE® Eye-Q Excimer Laser System labeling. ### V. DEVICE DESCRIPTION The ALLEGRETTO WAVE® Eye-Q Excimer Laser system is a scanning-spot excimer laser system used in refractive surgery for the treatment of refractive errors of the human eye. The system consists of a compact excimer laser with high pulse frequency, a galvanometer scanner for positioning the laser spot and a fast eye-tracker for determining PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 2 of 39 {2} eye position and laser beam direction. The integrated eye-tracker offers automatic centration of the ablation and tracking of eye movements. The three devices that are used to plan and perform the topography-guided LASIK treatments are the: - ALLEGRETTO WAVE EYE-Q® Laser System - ALLEGRO Topolyzer topography system - T-CAT software for treatment planning The T-CAT software constructs each treatment plan using the manifest refractive error, diagnostic data obtained from the ALLEGRO Topolyzer topography system, and manual user adjustments. Each T-CAT plan uses numerical algorithms to generate the ablation contour patterns to be used in T-CAT LASIK. The planned treatment is transferred to the notebook computer of the ALLEGRETTO WAVE® Eye-Q Excimer Laser System via media, such as an USB-stick. The Excimer Laser System software checks the treatment file for integrity and request final approval by the user. The T-CAT treatment planning software is a device option that requires specific software licensing. This involves requesting authorization from the device manufacturer for each specific ALLEGRO Topolyzer and the corresponding ALLEGRETTO WAVE EYE-Q® laser device. Devices that have not been authorized for use with each other cannot be used for topography-guided treatments. # VI. ALTERNATIVE PRACTICES AND PROCEDURES Alternative methods of correcting nearsightedness (myopia) with and without astigmatism include: glasses, contact lenses, phakic intraocular lenses (PIOLs), LASIK with another laser system, and photorefractive keratectomy (PRK). # VII. MARKETING HISTORY The ALLEGRETTO WAVE® Eye-Q Excimer Laser System, T-CAT software module, and the ALLEGRO Topolyzer have been marketed in the following countries: Austria, Australia, Bahrain, Belgium, Brazil, Canada, China, France, Germany, Great Britain, Greece, Hong Kong, India, Ireland, Israel, Italy, Japan, Korea, Lebanon, Mexico, Netherlands, Norway, Russia, Saudi Arabia, Singapore, Slovenia, Spain, Sri Lanka, Sweden, Switzerland, Egypt, Algeria, Argentina, Chile, Columbia, Curacao, Finland, Iran, Jordan, Kenya, La Reunion, Malaysia, New Zealand, Poland, Serbia, Slovakia, South Africa, Sweden, Taiwan, Thailand, Czech Republic, Dubai), and the United States. The ALLEGRETTO WAVE® Eye-Q Excimer Laser System, T-CAT software module, and the ALLEGRO Topolyzer have not been withdrawn from marketing for any reason relating to PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 3 of 39 {3} the safety and effectiveness of the devices. ### VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Potential adverse reactions associated with LASIK include: loss of best-spectacle corrected visual acuity, overcorrection, increase in refractive cylinder, worsening of patient complaints such as double vision and glare, sensitivity to bright lights, increased difficulty with night vision, fluctuations in vision, increase in intraocular pressure, corneal haze, corneal infection/infiltrate/ulcer, corneal epithelial defect, corneal decompensation/edema, problems associated with the flap including a lost, misplaced or misaligned flap, retinal detachment, and retinal vascular accidents. The occurrence of many of these events may involve secondary (additional) surgical intervention. Please refer to the complete list of adverse events and complications observed during the clinical study, which are presented in Section X below. ### IX. SUMMARY OF PRECLINICAL STUDIES #### A. Laboratory/Animal Studies No preclinical in-vivo studies were conducted or required to demonstrate safety and effectiveness. #### B. Additional Studies 1. Hazard Analysis and Software Validation. The system hazard analysis was updated to include hazards attributable to the ALLEGRO Topolyzer and to the T-CAT treatment planning software. All new hazards have been acceptably mitigated and the mitigations have been validated under the WaveLight quality system. Also, software validation and verification tests have been successfully completed for the ALLEGRETTO WAVE® Eye-Q Excimer Laser System, the T-CAT software module, and the ALLEGRO Topolyzer, and the current software versions have no unresolved anomalies. 2. Ablation Profilometry. Prior to the start of the clinical study, the T-CAT ablation algorithm was validated with profile measurements of representative plastic ablations spanning the entire dioptric range of spherical, cylindrical, and spherocylindrical treatments to be available for clinical use. For each test ablation, the results were depicted as profile plots of the measured and intended ablation and the percent difference. These results were consistently within ±10% of the intended ablation. PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 4 of 39 {4} ## **X. SUMMARY OF PRIMARY CLINICAL STUDY** The applicant performed a study (T-CAT-001) to establish reasonable assurance of the safety and effectiveness of T-CAT for performing topography-guided LASIK using the ALLEGRETTO WAVE® Eye-Q Excimer Laser System for the treatment of manifest and cornea-based myopic refractive errors under G090153. ### **A. Study Design** The T-CAT-001 study was a prospective, non-randomized, multicenter study conducted at nine (9) clinical sites. A total of 249 eyes of 212 enrolled subjects with myopia, with or without astigmatism, were treated with Topography-guided Custom Ablation Treatment (T-CAT) LASIK with the ALLEGRETTO WAVE® Eye-Q Excimer Laser System. The sample size for this study was based on having a high probability that the confidence interval for the mean refractive error is wholly contained in the interval (-0.5D, 0.5D). A sample size of 249 evaluable eyes was deemed sufficient to estimate the mean refractive error to within $\pm 0.5$ D. Corneal topography, manifest refraction, and measurements of uncorrected (UCVA) and best spectacle-corrected visual acuity (BSCVA) were obtained at baseline and at appropriate times after the LASIK treatment to evaluate the effectiveness of the treatment. Safety monitoring throughout the study included observations at all scheduled and unscheduled visits for subjective complaints, complications, and adverse events; as well as clinically significant findings upon ophthalmic examination, dilated fundus examination, slit lamp examination, and contrast sensitivity testing. Subject reported outcome questionnaires were used to evaluate subjective visual complaints, quality of vision, and quality of life preoperatively and postoperatively. Subjects who agreed to participate in the T-CAT-001 study provided informed consent and underwent the required screening procedures to determine study eligibility for T-CAT. Subjects in whom one or both eyes had a preoperative refractive error within the specified range for myopia (MRSE up to -9.0 D; sphere 0 to -9.0 D, cylinder 0 to 6.0 D) and met all study eligibility criteria were further evaluated as potential candidates for a topography-guided LASIK procedure. Measurements taken at baseline and postoperatively included manifest refraction, cycloplegic refraction, distance BSCVA and UCVA, slit lamp examination, corneal topography, pachymetry, intraocular pressure, and fundus examination. Corneal topographies used to plan the T-CAT LASIK treatment were obtained prior to treatment using the ALLEGRO Topolyzer topography system. The T-CAT software used data from the ALLEGRO Topolyzer and clinical refraction to determine the treatment plan; then, the topography-guided LASIK procedure was PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 5 of 39 {5} delivered to the study eye using the ALLEGRETTO WAVE® Eye-Q Excimer Laser System. # 1. Clinical Inclusion and Exclusion Criteria # Inclusion Criteria Subjects enrolled in the study were required to meet these conditions: be at least 18 years of age; a candidate for LASIK surgery with myopia at the spectacle plane ≤ -9.0 D manifest refraction spherical equivalent (MRSE), with sphere between 0.0 and -9.0 D and astigmatism between 0.0 and 6.0 D in the operative eye, and the operative eye targeted for emmetropia; have a reliable corneal topography that could be used to determine the T-CAT treatment plan, visual acuity correctable to 20/25 or better in each eye; if wearing contact lenses, discontinue use of soft lenses for at least 3 days, soft extended wear lenses for at least 1 week, soft toric lenses or rigid gas permeable lenses for at least 2 weeks; contact lens wearers must have had two manifest refractions taken at least one week apart that did not differ by more than 0.5 D; providing written informed consent; and, willing and able to comply with the follow-up visit schedule. # Exclusion Criteria Subjects who met any of these conditions were excluded from the study: history of prior refractive treatment; mixed astigmatism refractive error; clinically significant lenticular astigmatism, abnormal topography that would place the eye at risk for developing post-refractive corneal ectasia, such as keratoconus, keratoconus suspect, forme fruste keratoconus, or pellucid marginal degeneration; treatment plan would predict a residual stromal bed thickness less than 250 microns; history of herpes simplex keratitis, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, corneal dystrophy, or other corneal or anterior segment disease that might reasonably be expected to affect the outcome of treatment; evidence of retinal vascular disease; female patients who were pregnant or lactating or planned to become pregnant during the course of the study; known sensitivity to study medications; nystagmus or any other condition that would prevent a steady gaze during the LASIK treatment or other diagnostic tests; corneal dystrophy or corneal guttae; any pathology involving the iris, such as coloboma, tears, cuts, or significant pigment loss; other residual, recurrent or active ocular pathology or previous intraocular or corneal surgery that might confound the outcome or increase the risk of the study; any acute or chronic illness that might increase the risk or confound the outcome of the study, such as diagnosed autoimmune disease, systemic connective tissue disease, clinically significant atopic disease, uncontrolled diabetes mellitus; use of systemic corticosteroids or antimetabolites; intraocular pressure > 23 mm Hg, a history of glaucoma, or a glaucoma suspect; or, any other history, condition, or finding that would make the subject unsuitable as a candidate for LASIK or study participation or may confound the outcome of the study. PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 6 of 39 {6} ## 2. Follow-Up Schedule All subjects were evaluated at the following visit intervals before and after the T-CAT LASIK treatment: - Preoperative (-30 to -1 days) - Operative (Day 0) - Day 1 (1 to 3 days) - Week 1 (5 to 9 days) - Month 1 (3 to 5 weeks) - Month 3 (10 to 14 weeks) - Month 6 (21 to 26 weeks) - Month 9 (35 to 43 weeks) - Month 12 (11-14 months; Final Exam) All subjects were expected to return for each follow-up examination during the visit windows shown above. All final exam procedures were completed at the Month 12 visit. Preoperatively, the subjects' ocular, medical, and medication histories and demographic information were obtained. Objective parameters measured during the study included, uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), manifest refraction, cycloplegic refraction, intraocular pressure, corneal pachymetry, slit lamp examination of the anterior segment, fundus examination, corneal topography, central keratometry, aberrometry, low contrast acuity, and contrast sensitivity. Patient reported outcomes included a self-evaluation of visual symptoms, a quality of life questionnaire, and patient satisfaction with the T-CAT LASIK procedure. ## 3. Clinical Endpoints ### Safety and Effectiveness Criteria The primary safety target criteria for the study, evaluated at the time point of refractive stability are: - Changes in Best Spectacle Corrected Visual Acuity: Less than 5.0% of the eyes should lose 2 or more lines of BSCVA; and less than 1.0% of eyes that have preoperative BSCVA of 20/20 or better should have postoperative BSCVA worse than 20/40. - Incidence of Adverse Events: Less than 1% of eyes should have a specific adverse event (per type of event). - Induced Manifest Refractive Astigmatism: Less than 1% of eyes treated PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 7 of 39 {7} for spherical correction only should have an increase in manifest refractive astigmatism of more than 2.0 D of absolute cylinder magnitude as compared to the preoperative refraction. These primary safety endpoints were measured postoperatively at 1, 3, 6, 9 and 12-months. Specifically, safety outcomes at 3-months postoperatively were assessed, as refractive stability is reached by that time. Other safety endpoints included adverse events (AEs), complications, evaluation of corneal haze and intraocular pressure, symptoms/problems/complaints assessed in subject questionnaires and contrast sensitivity. The primary effectiveness target criteria for the study, evaluated at the postoperative time point of refractive stability, are: - Refractive Predictability: Decrease in MRSE to within ± 1.00 D and ± 0.50 D of the intended refractive outcome at the point at which stability is first reached. A minimum of 75% of eyes should have achieved a refraction within ± 1.00 D of the intended outcome, and at least 50% of eyes should be within ± 0.50 D of the intended outcome. - Visual Acuity: A minimum of 85% of eyes should have UCVA of 20/40 or better for eyes with BSCVA of 20/20 or better preoperatively. - Refractive Stability: A minimum of 95% of eyes should have a change of 1.00 D or less in MRSE between 2 refractions performed at two consecutive scheduled visit intervals performed at least 3 months apart, and the mean rate of MRSE change should be 0.04 D or less per month (NOTE: Refractive stability is generally accepted to have been achieved at the latter of two postoperative refractions performed at least 3 months apart or at 3 months after surgery when compared with the 1-month interval, if all of the refractive stability criteria have been met). Other effectiveness endpoints include an analysis of Zernike data and, and a patient symptom questionnaire that assesses vision related quality of life factors. These primary effectiveness endpoints were measured postoperatively at 1, 3, 6, 9, and 12-months. Specifically, effectiveness outcomes were assessed at 3-months postoperatively, as refractive stability is reached by that time. No retreatments were performed in the study. Therefore, no safety or effectiveness data are available for the use of T-CAT LASIK in performing a retreatment procedure or for T-CAT LASIK treated eyes that have a retreatment performed using another technology. ## B. Accountability of PMA Cohort PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 8 of 39 {8} Accountability by eye is summarized below in Table 1 for all 249 eyes of 212 enrolled subjects treated with T-CAT LASIK in the study. Accountability at each visit ranging from 95.0% to 100.0%. The accountability at the 12-month final visit is 95.0%. **Table 1: Accountability by Eye for All Eyes Treated for Myopia** | Status^{1} | 1 Day | | 1 Week | | 1 Month | | 3 Months | | 6 Months | | 9 Months | | 12 Months | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | 249 | | 249 | | 249 | | 249 | | 249 | | 249 | | 249 | | | | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | | Enrolled (N) | | | | | | | | | | | | | | | | Available for Analysis | 248 | 99.6 | 249 | 100 | 248 | 99.6 | 247 | 99.2 | 244 | 98.0 | 237 | 95.2 | 230 | 92.4 | | Discontinued | 0 | 0 | 0 | 0 | 1 | 0.4 | 1 | 0.4 | 1 | 0.4 | 2 | 0.8 | 7 | 2.8 | | Active (Not Eligible for Interval) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0.8 | 8 | 3.2 | 12 | 4.8 | | Missed Visit (Accounted for) | 1 | 0.4 | 0 | 0 | 0 | 0 | 1 | 0.4 | 2 | 0.8 | 2 | 0.8 | 0 | 0 | | Percent (%) Accountability | | 99.6 | | 100 | | 100 | | 99.6 | | 98.4 | | 96.0 | | 95.0 | N = Enrolled (total number of eyes that underwent a primary T-CAT LASIK treatment). Discontinued = Total number of eyes no longer under observation. Active = Total number of eyes that underwent a primary T-CAT LASIK treatment but had not reached the postoperative interval being reported. Lost to Follow-up (LTF) = Total number of eyes that failed to complete the specified examination interval and all subsequent examination intervals; includes eyes of subjects who moved, those who refused to come back for additional exams, and subjects who were contacted by telephone but did not complete any subsequent exams. Missed Visit = Total number of eyes that failed to undergo the specified examination interval but completed a subsequent visit. $$\% \text{ Accountability} = \frac{\text{Available for Analysis}}{\text{Enrolled} - \text{Discontinued} - \text{Not Yet Eligible}}$$ A total of 19 eyes in 17 subjects (19/249 eyes of 212 enrolled subjects; 7.6%) were considered to be discontinued or LTF (defined directly above) at the conclusion of the 12-month study. Four (4) were discontinued for administrative reasons, one (1) was a voluntary withdrawal, and the remainder (14 eyes) were lost-to-follow-up. BSCVA at PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 9 of 39 {9} last recorded visit was provided and was 20/20 or better in each of these 19 eyes of 17 subjects. ### C. Study Population Demographics and Baseline (Preoperative) Parameters #### Demographics Demographic characteristics of the subjects enrolled in the study are summarized in Table 2 below. The demographics of the study are typical for a contemporary refractive surgery clinical trial performed in the United States. Table 2: Summary of Demographic Information | Parameter | Myopia Cohort N=212 subjects (249 eyes) | | | | --- | --- | --- | --- | | | | n/N^{1} | % | | Gender | Male | 93 | 43.87% | | | Female | 119 | 56.13% | | Race | Caucasian | 157 | 74.06% | | | Asian | 8 | 3.77% | | | Black | 4 | 1.89% | | | Hispanic | 37 | 17.45% | | | Other | 6 | 2.83% | | Surgical Eye | Right | 128 | 51.41% | | | Left | 121 | 48.59% | | Age (in years) | Mean (std) | 34.0 (9.3) | | | | Min - Max | 18 - 65 | | $^{1}$ Gender, Race, and Age n/N's are based on the 212 subjects enrolled in the study that had eyes treated. Surgical Eye n/N is based on the total 249 eyes treated in the study. Age of the subjects in the T-CAT LASIK study ranged from 18 to 65 years, with a mean age of 34.0 years, at the time the T-CAT LASIK treatment was performed. The subject population consisted of an approximately equal number of male (44%) and female (56%) subjects. The study was performed at nine sites in the United States; and study subjects treated at research sites located in the Midwest or Southeast were mostly Caucasian, while subjects in the Southwest or West were primarily Caucasian or Hispanic. The eyes treated in the T-CAT-001 myopic study cohort were approximately equally distributed, with 128 (51%) right eyes treated and 121 (49%) left eyes treated. The age, race, and gender of each study site cohort were characteristic of the typical LASIK patient population of the site. #### Baseline Refractive Parameters The preoperative bin distribution, based on the preoperative manifest refraction at the spectacle plane that was used in calculating the T-CAT LASIK treatment plan, is summarized below, with stratification based on sphere and cylinder in Table 3 and on MRSE and cylinder in Table 4. Shaded areas of Tables 3 and 4 indicate refractive PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 10 of 39 {10} conditions that were studied. However, due to the limited number of subject studied for each bin that is shaded, treatment of these dioptic ranges (in both sphere and cylinder) are either flagged as warnings to the user or locked out in software to prevent use in treatment. All T-CAT treated eyes were targeted for emmetropia, with the measured pre-treatment clinical manifest refraction, as entered into the T-CAT software to calculate the treatment plan, used as the attempted refraction for the refractive predictability calculations. **Table 3: T-CAT-001 Bin Distribution Stratified by Attempted Sphere and Cylinder** | Attempted Sphere | Attempted Cylinder | | | | | | | | Total | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | 0.00D | -0.01 to -0.50 D | -0.51 to -1.00 D | -1.01 to -2.00 D | -2.01 to -3.00 D | -3.01 to -4.00 D^{1} | -4.01 to -5.00 D^{1} | -5.01 to -6.00 D^{2} | | | 0.00 to -1.00 D | 4 | 7 | 6 | 11 | 4 | 2 | 4 | 1 | 39 | | -1.01 to -2.00 D | 2 | 9 | 11 | 7 | 9 | 2 | 0 | 1 | 41 | | -2.01 to -3.00 D | 3 | 12 | 3 | 2 | 2 | 2 | 3 | 0 | 27 | | -3.01 to -4.00 D | 6 | 8 | 7 | 4 | 5 | 3 | 0 | 0 | 33 | | -4.01 to -5.00 D | 2 | 6 | 6 | 6 | 0 | 1 | 0 | 0 | 21 | | -5.01 to -6.00 D | 4 | 11 | 2 | 3 | 5 | 2 | 0 | 0 | 27 | | -6.01 to -7.00 D | 6 | 5 | 2 | 5 | 3 | 0 | 0 | 0 | 21 | | -7.01 to -8.00 D | 6 | 6 | 5 | 5 | 1 | 0 | 0 | 0 | 23 | | -8.01 to -9.00 D^{2} | 5 | 9 | 3 | 0 | 0 | 0 | 0 | 0 | 17 | | Total N | 38 | 73 | 45 | 43 | 29 | 12 | 7 | 2 | 249 | $^{1}$ Please note that treatment of these dioptic powers will present a flagged warning to the user so that the user understands that FDA believes correction of these powers has not been substantiated by an adequate set of data. $^{2}$ Please note that treatment of these refractive powers is not allowed because the number of subjects studied cannot substantiate the effectiveness of treatment of this dioptic range. **Table 4: T-CAT-001 Bin Distribution Stratified by Attempted MRSE and Cylinder** | Attempted MRSE | Attempted Cylinder | | | | | | | | Total | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | 0.00D | -0.01 to -0.50 D | -0.51 to -1.00 D | -1.01 to -2.00 D | -2.01 to -3.00 D | -3.01 to -4.00 D | -4.01 to -5.00 D | -5.01 to -6.00 D | | | 0.00 to -1.00 D | 4 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 8 | | -1.01 to -2.00 D | 2 | 11 | 9 | 11 | 4 | 0 | 0 | 0 | 37 | | -2.01 to -3.00 D | 3 | 10 | 7 | 6 | 8 | 3 | 2 | 1 | 40 | | -3.01 to -4.00 D | 6 | 12 | 6 | 2 | 3 | 2 | 2 | 0 | 33 | | -4.01 to -5.00 D | 2 | 5 | 6 | 7 | 5 | 1 | 2 | 1 | 29 | | -5.01 to -6.00 D | 4 | 9 | 4 | 5 | 0 | 3 | 1 | 0 | 26 | PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 11 of 39 {11} | Attempted Cylinder | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Attempted MRSE | 0.00D | -0.01 to -0.50 D | -0.51 to -1.00 D | -1.01 to -2.00 D | -2.01 to -3.00 D | -3.01 to -4.00 D | -4.01 to -5.00 D | -5.01 to -6.00 D | Total | | -6.01 to -7.00 D | 6 | 6 | 3 | 2 | 3 | 1 | 0 | 0 | 21 | | -7.01 to -8.00 D | 6 | 7 | 5 | 5 | 4 | 2 | 0 | 0 | 29 | | -8.01 to -9.00 D | 5 | 11 | 4 | 4 | 2 | 0 | 0 | 0 | 26 | | Total N | 38 | 73 | 45 | 43 | 29 | 12 | 7 | 2 | 249 | #### D. Safety and Effectiveness Results ##### Safety Results The safety analyses were based on the total PMA cohort of 249 eyes of 212 enrolled subjects. A summary of key safety and effectiveness variables at each of the postoperative visits is provided below in Table 5 for the myopia cohort. The primary safety outcomes for this study and overall AEs are presented below in the following tables. It should be noted that the safety of the device was not based on the study sample alone, but rather on all the available data from the device to date. The safety data from this study were for confirmatory purposes. **Table 5: Summary of Key Safety Parameters after T-CAT LASIK** | SAFETY VARIABLES | | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | | --- | --- | --- | --- | --- | --- | --- | | Loss of 2 or more lines BCVA^{1} | n/N | 1/248 | 0/247 | 1/244 | 0/237 | 1/230 | | | (%) | (0.40%) | (0.00%) | (0.41%) | (0.00%) | (0.43%) | | | (CI) | ( 0.0, 2.2) | ( 0.0, 1.5) | ( 0.0, 2.3) | ( 0.0, 1.5) | ( 0.0, 2.4) | | BCVA worse than 20/40 | n/N | 0/248 | 0/247 | 1/244 | 0/237 | 0/230 | | | (%) | (0.00%) | (0.00%) | (0.41%) | (0.00%) | (0.00%) | | | (CI) | ( 0.0, 1.5) | ( 0.0, 1.5) | ( 0.0, 2.3) | ( 0.0, 1.5) | ( 0.0, 1.6) | | Increase > 2D cylinder (spherical only) | n/N | 0/ 37 | 0/ 37 | 0/ 36 | 0/ 36 | 0/ 36 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | ( 0.0, 9.5) | ( 0.0, 9.5) | ( 0.0, 9.7) | ( 0.0, 9.7) | ( 0.0, 9.7) | | BCVA worse than 20/40 if 20/20 or better preop | n/N | 0/242 | 0/241 | 1/238 | 0/232 | 0/225 | | | (%) | (0.00%) | (0.00%) | (0.42%) | (0.00%) | (0.00%) | $^{1}$ Two additional eyes had single reports of transient loss of 2 or more lines of BSCVA at unscheduled visits. These eyes are reported as occurring at unscheduled visits in Table 8, 'Adverse Events for All Myopic Eyes Treated with T-CAT LASIK'. Loss of BSCVA was minimal, with only 5 single reports of BSCVA loss of 2 lines or more at any of the 1 month or later, scheduled or unscheduled, postoperative visits in the study. All five of these instances of BSCVA loss were transient, unrelated to the T-CAT LASIK treatment and resolved by the next postoperative follow-up visit. The key safety parameters at 3 months after T-CAT LASIK (the time point of refractive stability), stratified by each preoperative MRSE dioptic bin and by each PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 12 of 39 {12} preoperative cylinder bin, are presented below in Tables 6 and 7, respectively. Similar safety results are observed in the stratified bins as are seen in the entire cohort. Thus, the clinical safety outcomes support the refractive range for the approved indications for use. **Table 6: Summary of Key Safety Parameters Stratified by Pre-Treatment MRSE - Results at 3 Months after T-CAT LASIK** | SAFETY VARIABLES | | -0.01 TO -1.00D | -1.01 TO -2.00D | -2.01 TO -3.00D | -3.01 TO -4.00D | -4.01 TO -5.00D | -5.01 TO -6.00D | -6.01 TO -7.00D | -7.01 TO -8.00D | -8.01 TO -9.00D | CUM TOTAL | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Loss of 2 or more lines BCVA | n/N | 0/ 8 | 0/ 37 | 0/ 40 | 0/ 33 | 0/ 28 | 0/ 26 | 0/ 20 | 0/ 29 | 0/ 26 | 0/247 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (0.0, 36.9) | (0.0, 9.5) | (0.0, 8.8) | (0.0, 10.6) | (0.0, 12.3) | (0.0, 13.2) | (0.0, 16.8) | (0.0, 11.9) | (0.0, 13.2) | (0.0, 1.5) | | BCVA worse than 20/40 | n/N | 0/ 8 | 0/ 37 | 0/ 40 | 0/ 33 | 0/ 28 | 0/ 26 | 0/ 20 | 0/ 29 | 0/ 26 | 0/247 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (0.0, 36.9) | (0.0, 9.5) | (0.0, 8.8) | (0.0, 10.6) | (0.0, 12.3) | (0.0, 13.2) | (0.0, 16.8) | (0.0, 11.9) | (0.0, 13.2) | (0.0, 1.5) | | Increase > 2D cylinder | n/N | 0/ 4 | 0/ 2 | 0/ 3 | 0/ 6 | 0/ 2 | 0/ 4 | 0/ 5 | 0/ 6 | 0/ 5 | 0/ 37 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (0.0, 60.2) | (0.0, 84.2) | (0.0, 70.8) | (0.0, 45.9) | (0.0, 84.2) | (0.0, 60.2) | (0.0, 52.2) | (0.0, 45.9) | (0.0, 52.2) | (0.0, 9.5) | | BCVA worse than 20/40 if 20/20 or better preop | n/N | 0/ 8 | 0/ 37 | 0/ 40 | 0/ 32 | 0/ 28 | 0/ 25 | 0/ 19 | 0/ 26 | 0/ 26 | 0/241 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (0.0, 36.9) | (0.0, 9.5) | (0.0, 8.8) | (0.0, 10.9) | (0.0, 12.3) | (0.0, 13.7) | (0.0, 17.6) | (0.0, 13.2) | (0.0, 13.2) | (0.0, 1.5) | **Table 7: Summary of Key Safety Parameters Stratified by Pre-Treatment Cylinder - Results at 3 Months after T-CAT LASIK** | SAFETY VARIABLES | | 0.00D | 0.01 TO 0.50D | 0.51 TO 1.00D | 1.01 TO 2.00D | 2.01 TO 3.00D | 3.01 TO 4.00D | 4.01 TO 5.00D | 5.01 to 6.00D | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Loss of 2 or more lines BCVA | n/N | 0/ 37 | 0/ 72 | 0/ 45 | 0/ 43 | 0/ 29 | 0/ 12 | 0/ 7 | 0/ 2 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | ( 0.0, 9.5) | ( 0.0, 5.0) | ( 0.0, 7.9) | ( 0.0, 8.2) | ( 0.0, 11.9) | ( 0.0, 26.5) | ( 0.0, 41.0) | ( 0.0, 84.2) | | BCVA worse than 20/40 | n/N | 0/ 37 | 0/ 72 | 0/ 45 | 0/ 43 | 0/ 29 | 0/ 12 | 0/ 7 | 0/ 2 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | ( 0.0, 9.5) | ( 0.0, 5.0) | ( 0.0, 7.9) | ( 0.0, 8.2) | ( 0.0, 11.9) | ( 0.0, 26.5) | ( 0.0, 41.0) | ( 0.0, 84.2) | | Increase > 2D cylinder | n/N | 0/ 37 | 0/ 0 | 0/ 0 | 0/ 0 | 0/ 0 | 0/ 0 | 0/ 0 | 0/ 0 | | | (%) | (0.00%) | | | | | | | | | | (CI) | ( 0.0, 9.5) | | | | | | | | | BCVA worse than 20/40 if 20/20 or better preop | n/N | 0/ 37 | 0/ 70 | 0/ 45 | 0/ 42 | 0/ 28 | 0/ 10 | 0/ 7 | 0/ 2 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | ( 0.0, 9.5) | ( 0.0, 5.1) | ( 0.0, 7.9) | ( 0.0, 8.4) | ( 0.0, 12.3) | ( 0.0, 30.8) | ( 0.0, 41.0) | ( 0.0, 84.2) | Corneal Haze PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 13 of 39 {13} Corneal haze was graded at each postoperative time point after observation on the slit lamp examination. Rare occurrences of haze were reported in the T-CAT) LASIK clinical trial. # Intraocular Pressure Intraocular pressure was measured by Goldmann applanation tonometry at the slit lamp. There were no clinically significant changes (defined as >10 mm Hg increases) between intraocular pressure measurements obtained preoperatively and postoperatively. Adverse events and complications that occurred during the study at all scheduled and unscheduled visits are presented in Table 8 below. The cumulative rate of safety events classified as adverse events that occurred at scheduled or unscheduled visits was 1.6% (4/249 eyes) for BSCVA loss of 2 or more lines, all of which were transient and unrelated to the T-CAT LASIK procedure. The cumulative rate of retinal detachments was 0.8% (2/244 eyes), occurring bilaterally in the same subject at approximately 6 months after the T-CAT LASIK surgery; both of which were unrelated to the T-CAT LASIK treatment. PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 14 of 39 {14} **Table 8: Adverse Events for All Myopic Eyes Treated with T-CAT LASIK$^{1}$** | ADVERSE EVENTS | Intraop (N=249) | Day 1 (N=248) | Week 1 (N=249) | Month 1 (N=248) | Month 3 (N=247) | Month 6 (N=244) | Month 9 (N=237) | Month 12 (N=230) | Unscheduled (n) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Diffuse lamellar keratitis with progressive melt | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Corneal infiltrate or ulcer | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Any corneal epithelial defect involving keratectomy site at 1 month or later | | | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Corneal edema at 1 month or later | | | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Epithelium in interface with loss of 2 or more lines of BSCVA | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Miscreated flap (lost, incomplete, too thin) | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Melting of the flap | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | IOP on 2 consecutive exams that is > 10 mm Hg above baseline or > 30 mm Hg | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Haze beyond 6 mos. with loss of ≥2 lines (≥10 letters) BSCVA | | | | | | | 0 (0.00%) | 0 (0.00%) | 0 | | Decrease of BSCVA of ≥ 10 letters | | | | | 0 (0.00%) | 1(0.41%) | 0 (0.00%) | 1(0.43%) | 2 | | Retinal detachment | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 2(0.82%) | 0 (0.00%) | 0 (0.00%) | 0 | | Retinal vascular accidents | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Any other vision threatening event | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Ocular penetration | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | $^{1}$ BSCVA loss, n = 2 new reports occurring at unscheduled visits. {15} ### Complications Complications that occurred during the study at all scheduled and unscheduled visits are presented in Table 9 below. The following complications were observed at 3 months after T-CAT LASIK surgery: foreign body sensation at 1 month or later, 5 eyes (2.0%); double images in the treated eye, 1 eye (0.4%); ghost images in the treated eye, 2 eyes (0.8%); dry eyes requiring prescribed use of ocular lubricants or punctal plugs, 10 eyes (4.0%). At the final 12-month postoperative study visit, the safety observations of any type that occurred at a rate of 1% or greater included reports of: dry eye requiring no treatment or ocular lubricants as needed in 20 eyes (8.7%), blurred vision at distance or near in 6 eyes (2.6%), mild superficial punctate keratitis in 4 eyes (1.7%), ocular irritation in 4 eyes (1.4%), dry eyes requiring punctal plugs or prescribed use of ocular lubricants in 3 eyes (1.3%), fluctuation in vision in 3 eyes (1.3%), and starbursts in 3 eyes (1.3%). **Table 9: Complications for All Myopic Eyes Treated with T-CAT LASIK** | COMPLICATIONS | Intraop (N=249) | Day 1 (N=248) | Week 1 (N=249) | Month 1 (N=248) | Month 3 (N=247) | Month 6 (N=244) | Month 9 (N=237) | Month 12 (N=230) | Unscheduled^{1} (n) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Corneal edema between 1 week and 1 month after procedure | | | 1 (0.40%) | 0 (0.00%) | | | | | 0 | | Peripheral corneal epithelial defect at 1 month or later | | | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Epithelium in interface, >2mm | | | | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Foreign body sensation at 1 month or later | | | | 6 (2.42%) | 5 (2.02%) | 3 (1.23%) | 0 (0.00%) | 0 (0.00%) | 1 | | Pain at 1 month or later | | | | 2 (0.81%) | 0 (0.00%) | 0 (0.00%) | 2 (0.84%) | 0 (0.00%) | 0 | | Double images in the operative eye | | 0 (0.00%) | 0 (0.00%) | 2 (0.81%) | 1 (0.40%) | 1 (0.41%) | 2 (0.84%) | 0 (0.00%) | 1 | | Ghost images in the operative eye | | 0 (0.00%) | 1 (0.40%) | 2 (0.81%) | 2 (0.81%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 2 | | Flap is not of the size and shape as initially intended or microkeratome stopped mid-cut or resultant flap is misaligned | 0 (0.00%) | 2 (0.80%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 | | Diffuse lamellar keratitis | | 5 (2.01%) | 2 (0.80%) | 1 (0.40%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 0 (0.00%) | 4 | | Dry eyes requiring punctal plugs or prescribed use of ocular lubricants at 3 months or later | | | | | 10 (4.05%) | 8 (3.28%) | 6 (2.53%) | 3 (1.30%) | 6 | $^{1}$ Double images, new report n=1; Ghost images, new report n = 2; Diffuse lamellar keratitis, new report n = 1, ongoing reports n = 3; Dry eyes with treatment, new reports n = 4, ongoing reports n = 2. {16} ## Patient Subjective Questionnaire Table 10 below summarizes the severity of visual symptoms after T-CAT LASIK. Responses were obtained from each subject using a 12-item, self-administered, subjective symptom questionnaire (labeled “Patient Questionnaire” on patient forms in G090153). Visual symptoms after T-CAT LASIK were generally mild in severity. **Table 10: Visual Symptoms Recorded via Self-Administered Symptom Questionnaire$^{1}$** | Question | Visit | None | Mild | Moderate | Marked | Severe | | --- | --- | --- | --- | --- | --- | --- | | Light Sensitivity | Screening | 136/249 (55%) | 71/249 (29%) | 29/249 (12%) | 13/249 (5%) | | | | Postop Month 1 | 77/247 (31%) | 110/247 (45%) | 40/247 (16%) | 17/247 (7%) | 3/247 (1%) | | | Postop Month 3 | 125/247 (51%) | 83/247 (34%) | 35/247 (14%) | 1/247 (0%) | 3/247 (1%) | | | Postop Month 6 | 141/244 (58%) | 85/244 (35%) | 17/244 (7%) | 1/244 (0%) | | | | Postop Month 9 | 144/237 (61%) | 81/237 (34%) | 12/237 (5%) | | | | | Postop Month 12 | 160/230 (70%) | 56/230 (24%) | 14/230 (6%) | | | | Difficulty Driving at Night | Screening | 112/249 (45%) | 81/249 (33%) | 35/249 (14%) | 18/249 (7%) | 3/249 (1%) | | | Postop Month 1 | 130/246 (53%) | 76/246 (31%) | 25/246 (10%) | 11/246 (4%) | 4/246 (2%) | | | Postop Month 3 | 148/247 (60%) | 73/247 (30%) | 16/247 (6%) | 9/247 (4%) | 1/247 (0%) | | | Postop Month 6 | 179/244 (73%) | 43/244 (18%) | 17/244 (7%) | 5/244 (2%) | | | | Postop Month 9 | 166/236 (70%) | 56/236 (24%) | 12/236 (5%) | 2/236 (1%) | | | | Postop Month 12 | 164/230 (71%) | 51/230 (22%) | 14/230 (6%) | 1/230 (0%) | | | Reading Difficulty | Screening | 172/249 (69%) | 38/249 (15%) | 14/249 (6%) | 11/249 (4%) | 14/249 (6%) | | | Postop Month 1 | 190/247 (77%) | 24/247 (10%) | 19/247 (8%) | 10/247 (4%) | 4/247 (2%) | | | Postop Month 3 | 208/247 (84%) | 23/247 (9%) | 7/247 (3%) | 8/247 (3%) | 1/247 (0%) | | | Postop Month 6 | 205/244 (84%) | 26/244 (11%) | 7/244 (3%) | 5/244 (2%) | 1/244 (0%) | | | Postop Month 9 | 201/237 (85%) | 26/237 (11%) | 3/237 (1%) | 3/237 (1%) | 4/237 (2%) | | | Postop Month 12 | 194/230 (84%) | 29/230 (13%) | 4/230 (2%) | 2/230 (1%) | 1/230 (0%) | | Double Vision | Screening | 226/249 (91%) | 14/249 (6%) | 6/249 (2%) | 3/249 (1%) | | | | Postop Month 1 | 226/247 (91%) | 14/247 (6%) | 4/247 (2%) | 3/247 (1%) | | | | Postop Month 3 | 228/247 (92%) | 13/247 (5%) | 1/247 (0%) | 5/247 (2%) | | | | Postop Month 6 | 224/244 (92%) | 15/244 (6%) | 1/244 (0%) | 4/244 (2%) | | | | Postop Month 9 | 224/237 (95%) | 8/237 (3%) | 2/237 (1%) | 3/237 (1%) | | | | Postop Month 12 | 217/230 (94%) | 12/230 (5%) | 1/230 (0%) | | | | Fluctuation in Vision | Screening | 197/249 (79%) | 39/249 (16%) | 9/249 (4%) | 3/249 (1%) | 1/249 (0%) | | | Postop Month 1 | 130/247 (53%) | 89/247 (36%) | 21/247 (9%) | 6/247 (2%) | 1/247 (0%) | | | Postop Month 3 | 168/246 (68%) | 69/246 (28%) | 8/246 (3%) | 1/246 (0%) | | | | Postop Month 6 | 172/244 (70%) | 59/244 (24%) | 12/244 (5%) | 1/244 (0%) | | | | Postop Month 9 | 167/237 (70%) | 61/237 (26%) | 8/237 (3%) | 1/237 (0%) | | | | Postop Month 12 | 169/230 (73%) | 54/230 (23%) | 7/230 (3%) | | | PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 17 of 39 {17} | Question | Visit | None | Mild | Moderate | Marked | Severe | | --- | --- | --- | --- | --- | --- | --- | | Glare | Screening | 156/249 (63%) | 51/249 (20%) | 30/249 (12%) | 10/249 (4%) | 2/249 (1%) | | | Postop Month 1 | 107/247 (43%) | 113/247 (46%) | 21/247 (9%) | 6/247 (2%) | | | | Postop Month 3 | 142/247 (57%) | 90/247 (36%) | 13/247 (5%) | 2/247 (1%) | | | | Postop Month 6 | 148/244 (61%) | 85/244 (35%) | 11/244 (5%) | | | | | Postop Month 9 | 166/237 (70%) | 65/237 (27%) | 6/237 (3%) | | | | | Postop Month 12 | 153/230 (67%) | 75/230 (33%) | 2/230 (1%) | | | | Halos | Screening | 184/249 (74%) | 40/249 (16%) | 17/249 (7%) | 6/249 (2%) | 2/249 (1%) | | | Postop Month 1 | 100/247 (40%) | 101/247 (41%) | 32/247 (13%) | 11/247 (4%) | 3/247 (1%) | | | Postop Month 3 | 147/247 (60%) | 81/247 (33%) | 17/247 (7%) | 2/247 (1%) | | | | Postop Month 6 | 158/244 (65%) | 79/244 (32%) | 7/244 (3%) | | | | | Postop Month 9 | 175/237 (74%) | 55/237 (23%) | 7/237 (3%) | | | | | Postop Month 12 | 173/230 (75%) | 54/230 (23%) | 3/230 (1%) | | | | Starbursts | Screening | 189/249 (76%) | 34/249 (14%) | 18/249 (7%) | 6/249 (2%) | 2/249 (1%) | | | Postop Month 1 | 144/245 (59%) | 69/245 (28%) | 27/245 (11%) | 3/245 (1%) | 2/245 (1%) | | | Postop Month 3 | 179/247 (72%) | 54/247 (22%) | 11/247 (4%) | 3/247 (1%) | | | | Postop Month 6 | 183/244 (75%) | 57/244 (23%) | 3/244 (1%) | 1/244 (0%) | | | | Postop Month 9 | 193/237 (81%) | 37/237 (16%) | 6/237 (3%) | 1/237 (0%) | | | | Postop Month 12 | 186/229 (81%) | 36/229 (16%) | 6/229 (3%) | 1/229 (0%) | | | Dryness | Screening | 120/249 (48%) | 85/249 (34%) | 32/249 (13%) | 11/249 (4%) | 1/249 (0%) | | | Postop Month 1 | 41/247 (17%) | 135/247 (55%) | 49/247 (20%) | 18/247 (7%) | 4/247 (2%) | | | Postop Month 3 | 57/247 (23%) | 145/247 (59%) | 37/247 (15%) | 6/247 (2%) | 2/247 (1%) | | | Postop Month 6 | 90/244 (37%) | 113/244 (46%) | 35/244 (14%) | 5/244 (2%) | 1/244 (0%) | | | Postop Month 9 | 91/237 (38%) | 113/237 (48%) | 27/237 (11%) | 3/237 (1%) | 3/237 (1%) | | | Postop Month 12 | 114/230 (50%) | 92/230 (40%) | 18/230 (8%) | 6/230 (3%) | | | Pain | Screening | 236/249 (95%) | 9/249 (4%) | 3/249 (1%) | 1/249 (0%) | | | | Postop Month 1 | 214/247 (87%) | 26/247 (11%) | 7/247 (3%) | | | | | Postop Month 3 | 229/247 (93%) | 18/247 (7%) | | | | | | Postop Month 6 | 232/243 (95%) | 10/243 (4%) | 1/243 (0%) | | | | | Postop Month 9 | 221/237 (93%) | 15/237 (6%) | 1/237 (0%) | | | | | Postop Month 12 | 218/230 (95%) | 10/230 (4%) | 1/230 (0%) | 1/230 (0%) | | | Foreign Body Sensation | Screening | 211/249 (85%) | 28/249 (11%) | 9/249 (4%) | 1/249 (0%) | | | | Postop Month 1 | 174/246 (71%) | 61/246 (25%) | 7/246 (3%) | 1/246 (0%) | 3/246 (1%) | | | Postop Month 3 | 195/247 (79%) | 42/247 (17%) | 8/247 (3%) | 2/247 (1%) | | | | Postop Month 6 | 205/244 (84%) | 35/244 (14%) | 4/244 (2%) | | | | | Postop Month 9 | 208/237 (88%) | 27/237 (11%) | 1/237 (0%) | 1/237 (0%) | | | | Postop Month 12 | 208/229 (91%) | 16/229 (7%) | 5/229 (2%) | | | | Other | Screening | 5/ 10 (50%) | 2/ 10 (20%) | 1/ 10 (10%) | | 2/ 10 (20%) | | | Postop Month 1 | | 2/ 2 (100%) | | | | PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 18 of 39 {18} | Question | Visit | None | Mild | Moderate | Marked | Severe | | --- | --- | --- | --- | --- | --- | --- | | | Postop Month 3 | 2/ 3 (67%) | 1/ 3 (33%) | | | | | | Postop Month 6 | 7/ 10 (70%) | 2/ 10 (20%) | 1/ 10 (10%) | | | | | Postop Month 9 | 9/ 11 (82%) | | 2/ 11 (18%) | | | | | Postop Month 12 | 12/ 14 (86%) | 2/ 14 (14%) | | | | $^{1}$Any variation in the N for an observation at a specific time point is due to one or more subjects omitting the rating for that symptom at that time point. Changes in the degree of severity of visual symptoms reported via the visual symptom questionnaire at 3 months compared to baseline are summarized below in Table 11. All categories of complaints showed a reduction in severity after the T-CAT LASIK procedure compared to baseline, except double vision and foreign body sensation, both of which had a minimal increase in severity postoperatively. The 3.6% decrease in severity of light sensitivity, 4.4% decrease in complaints of difficulty driving at night, 6.4% decrease in reading difficulty, and 2.4% reduction in glare complaints were all statistically significant improvements in the severity of these visual symptoms in the T-CAT LASIK treated eyes. **Table 11: Changes in Degree of Severity of Visual Symptoms in All Eyes Treated with T-CAT LASIK** | Question | Percent Baseline None – Moderate | Percent Baseline Marked - Severe | Percent 3 Month None - Moderate | Percent 3 Month Marked - Severe | Difference in Marked - Severe | | --- | --- | --- | --- | --- | --- | | Light Sensitivity | 94.78 | 5.22 | 98.38 | 1.62 | -3.60 | | Difficulty Driving at Night | 91.57 | 8.43 | 95.95 | 4.05 | -4.39 | | Reading Difficulty | 89.96 | 10.04 | 96.36 | 3.64 | -6.40 | | Double Vision | 98.80 | 1.20 | 97.98 | 2.02 | 0.82 | | Fluctuation in Vision | 98.39 | 1.61 | 99.59 | 0.41 | -1.20 | | Glare | 95.18 | 4.82 | 99.19 | 0.81 | -4.01 | | Halos | 96.79 | 3.21 | 99.19 | 0.81 | -2.40 | | Starbursts | 96.79 | 3.21 | 98.79 | 1.21 | -2.00 | | Dryness | 95.18 | 4.82 | 96.76 | 3.24 | -1.58 | | Pain | 99.60 | 0.40 | 100.0 | 0.00 | -0.40 | | Foreign Body Sensation | 99.60 | 0.40 | 99.19 | 0.81 | 0.41 | | Other | 80.00 | 20.00 | 100.0 | 0.00 | -20.0 | **Table 12: Change in Refractive Status Vision Profile (RSVP) Score$^{1}$** PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 19 of 39 {19} | Visit | Subscale | N Diff | Mean Base | Mean Score | Mean Diff | Effect Size | | --- | --- | --- | --- | --- | --- | --- | | Postop Month 1 | Concern | 211 | 45.69 | 18.50 | -27.19 | -1.3178 | | | Expectations | 208 | 59.44 | 63.10 | 3.67 | 0.1450 | | | Physical/social functioning | 177 | 17.55 | 5.11 | -12.44 | -0.6409 | | | Driving | 177 | 23.26 | 13.82 | -9.44 | -0.4100 | | | Symptoms | 176 | 14.40 | 12.42 | -1.98 | -0.1288 | | | Optical problems | 174 | 7.54 | 5.63 | -1.90 | -0.1596 | | | Glare | 176 | 14.80 | 16.67 | 1.87 | 0.1203 | | | Problem with corrective lenses | 25 | 24.12 | 22.94 | -1.18 | -0.0685 | | | Total Score | 211 | 19.98 | 4.03 | -15.96 | -1.3233 | | Postop Month 3 | Concern | 210 | 45.65 | 13.87 | -31.78 | -1.5374 | | | Expectations | 205 | 59.33 | 65.24 | 5.91 | 0.2347 | | | Physical/social functioning | 198 | 16.46 | 3.44 | -13.02 | -0.7505 | | | Driving | 196 | 22.62 | 11.08 | -11.54 | -0.5140 | | | Symptoms | 195 | 14.08 | 8.63 | -5.45 | -0.3780 | | | Optical problems | 196 | 7.49 | 4.15 | -3.34 | -0.2761 | | | Glare | 195 | 14.79 | 12.54 | -2.24 | -0.1425 | | | Problem with corrective lenses | 26 | 26.67 | 12.02 | -14.65 | -0.9796 | | | Total Score | 210 | 19.97 | 3.99 | -15.97 | -1.3218 | | Postop Month 6 | Concern | 207 | 45.57 | 12.26 | -33.31 | -1.6213 | | | Expectations | 205 | 59.39 | 63.54 | 4.15 | 0.1638 | | | Physical/social functioning | 200 | 16.18 | 3.18 | -13.00 | -0.7606 | | | Driving | 200 | 22.38 | 10.38 | -12.00 | -0.5418 | | | Symptoms | 199 | 13.97 | 7.34 | -6.62 | -0.4457 | | | Optical problems | 198 | 7.66 | 3.61 | -4.05 | -0.3140 | | | Glare | 198 | 14.73 | 10.04 | -4.69 | -0.2891 | | | Problem with corrective lenses | 32 | 26.84 | 1.17 | -25.67 | -1.5522 | | | Total Score | 207 | 19.93 | 3.87 | -16.06 | -1.3354 | | Postop Month 9 | Concern | 201 | 45.46 | 12.73 | -32.73 | -1.5937 | | | Expectations | 197 | 59.64 | 64.21 | 4.57 | 0.1795 | | | Physical/social functioning | 191 | 16.31 | 3.16 | -13.15 | -0.7585 | | | Driving | 188 | 22.03 | 9.69 | -12.34 | -0.5628 | | | Symptoms | 190 | 14.02 | 6.99 | -7.03 | -0.4675 | | | Optical problems | 190 | 7.95 | 3.00 | -4.95 | -0.3742 | | | Glare | 191 | 15.01 | 8.40 | -6.61 | -0.4034 | | | Problem with corrective lenses | 38 | 28.60 | 2.96 | -25.64 | -1.3174 | | | Total Score | 201 | 19.89 | 3.64 | -16.25 | -1.3439 | | Postop Month 12 | Concern | 195 | 44.89 | 11.18 | -33.71 | -1.6601 | | | Expectations | 193 | 59.26 | 65.35 | 6.09 | 0.2403 | | | Physical/social functioning | 189 | 16.41 | 2.27 | -14.14 | -0.7807 | | | Driving | 188 | 22.03 | 8.29 | -13.74 | -0.6184 | | | Symptoms | 188 | 13.64 | 5.87 | -7.77 | -0.5237 | | | Optical problems | 188 | 7.22 | 2.65 | -4.57 | -0.3592 | | | Glare | 190 | 14.71 | 7.26 | -7.46 | -0.4563 | | | Problem with corrective lenses | 37 | 27.86 | 3.04 | -24.82 | -1.1559 | | | Total Score | 195 | 19.54 | 3.15 | -16.39 | -1.3822 | $^{1}$ The number of respondents (N) for each subscale varies based on whether the subscale question applies to that subject. The RSVP (Table 12 above) shows an improvement in all subscales evaluated at each of the postoperative visits and in the total composite score that is computed for each visit. The only exception is glare at the 1 month visit, which shows a worsening that changes to improvement at 3 months and all subsequent visits. Published literature indicates that a difference of 6 points or more on the composite PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 20 of 39 {20} score is a clinically significant change.$^{1}$ The difference in composite score from baseline to each postoperative visit showed a clinically significant improvement in the RSVP profile, with a mean improvement that is nearly three times the minimum threshold for clinically significant improvement at each postoperative visit, ranging from a change of -15.97 points at 3 months to a change of -16.39 points at 12 months. On the basis of these data, the T-CAT LASIK treatment leads to a clinically and statistically significant improvement in symptoms measured by the RSVP. Specifically, subjects who underwent T-CAT LASIK with the ALLEGRETTO WAVE$^{®}$ Eye-Q Excimer Laser in the clinical trial experienced an improvement in physical/social functioning, driving, visual symptoms, optical problems, and problems with corrective lenses that was evident at three months and continued to improve through 12 months postoperatively, compared to their habitual refractive correction method (glasses or contact lenses) preoperatively. A question to evaluate the study subjects self-reported satisfaction with the T-CAT LASIK procedure was added during the course of the study. Of the 124 subjects who were polled, nearly all of the study subjects (122/124; 98.4%) were satisfied with their outcomes and would have the T-CAT LASIK treatment again. #### Contrast Sensitivity Contrast sensitivity was evaluated preoperatively and at 3 and 6 months after the T-CAT LASIK procedure under mesopic (3 cd/m$^{2}$) and photopic (85 cd/m$^{2}$) chart luminance, with and without glare (1 lux and 10 lux for mesopic and photopic, respectively). Testing was performed using sine-wave grating targets with five spatial frequencies (1.5, 3, 6, 9, and 18 cycles/degree) and nine contrast levels. Clinically significant changes in contrast sensitivity, at 3 and 6 months after T-CAT LASIK, are summarized in Table 13 below. A clinically significant increase or decrease in contrast sensitivity is defined as an increase or decrease of at least 0.3 log units at two or more spatial frequencies. In addition, any transition from seeing to not seeing, or, from not seeing to seeing a grating at the highest available contrast is considered equivalent to a $\geq 0.3$ log unit change for the purpose of assessing clinical significance. As shown in Table 13, the number of T-CAT LASIK treated eyes with a clinically significant increase in contrast sensitivity was two to three folds higher than those eyes with clinically significant decreases, both with and without glare under mesopic and photopic testing conditions at 3 and 6 months postoperatively. **Table 13: Clinically Significant Changes in Log$_{10}$ Mesopic and Photopic Contrast Sensitivity (Log$_{10}$ [Threshold Contrast$^{-1}$]) With and Without Glare at 3 Months and 6 Months after T-CAT LASIK** PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 21 of 39 {21} | Visit | Luminance | Glare | Clinically Significant Decrease (n/N %) | Clinically Significant Increase (n/N %) | | --- | --- | --- | --- | --- | | Postop Month 3 | Mesopic | Glare | 25/ 210 (11.90) | 50/ 210 (23.81) | | | | No Glare | 15/ 210 ( 7.14) | 43/ 210 (20.48) | | | Photopic | Glare | 18/ 210 ( 8.57) | 58/ 210 (27.62) | | | | No Glare | 19/ 210 ( 9.05) | 55/ 210 (26.19) | | Postop Month 6 | Mesopic | Glare | 31/ 207 (14.98) | 68/ 207 (32.85) | | | | No Glare | 16/ 207 ( 7.73) | 52/ 207 (25.12) | | | Photopic | Glare | 20/ 207 ( 9.66) | 65/ 207 (31.40) | | | | No Glare | 17/ 207 ( 8.21) | 66/ 207 (31.88) | As shown in Tables 14 and 15, at 3 and 6 months after T-CAT LASIK surgery, there was an improvement in contrast sensitivity at nearly all low, middle, and high spatial frequencies under mesopic and photopic conditions, with and without glare PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 22 of 39 {22} **Table 14: Changes in Log$_{10}$ Mesopic and Photopic Contrast Sensitivity (Log$_{10}$ [Threshold Contrast$^{-1}$]) Without Glare at 3 Months and 6 Months after T-CAT LASIK$^{1}$** | Visit | Type | Cycles per Degree | Total N | Preop n | PreOp N_{0} | Preop Mean^{2} | Preop SD | Postop n | Visit N_{0} | Postop Mean^{3} | Postop SD | Paired Difference n | Difference N_{0} | Paired Difference Mean^{4} | Paired Difference SD | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Postop Month 3 | Mesopic | (1.5) | 247 | 245 | 1 | 1.6019 | 0.2323 | 245 | 0 | 1.6609 | 0.2521 | 243 | 1 | 0.0613 | 0.1806 | | | | (3) | 247 | 245 | 1 | 1.6116 | 0.3450 | 245 | 0 | 1.6546 | 0.3778 | 243 | 1 | 0.0372 | 0.4946 | | | | (6) | 247 | 240 | 6 | 1.7107 | 0.2718 | 245 | 0 | 1.7850 | 0.2539 | 239 | 6 | 0.0828 | 0.2512 | | | | (12) | 247 | 213 | 33 | 1.3893 | 0.2947 | 228 | 17 | 1.4017 | 0.3005 | 204 | 41 | 0.0430 | 0.3096 | | | | (18) | 247 | 166 | 79 | 1.0022 | 0.2972 | 178 | 67 | 1.0205 | 0.2830 | 135 | 109 | 0.0371 | 0.3310 | | | Photopic | (1.5) | 247 | 237 | 0 | 1.5969 | 0.2408 | 245 | 0 | 1.6379 | 0.2271 | 235 | 0 | 0.0435 | 0.1937 | | | | (3) | 247 | 236 | 1 | 1.6223 | 0.3755 | 245 | 0 | 1.6835 | 0.4092 | 234 | 1 | 0.0681 | 0.4870 | | | | (6) | 247 | 235 | 2 | 1.7995 | 0.2453 | 245 | 0 | 1.9140 | 0.2223 | 233 | 2 | 0.1132 | 0.2120 | | | | (12) | 247 | 230 | 7 | 1.4752 | 0.2840 | 242 | 3 | 1.6134 | 0.2581 | 226 | 10 | 0.1371 | 0.2876 | | | | (18) | 247 | 202 | 34 | 1.0924 | 0.2939 | 229 | 16 | 1.2167 | 0.3054 | 192 | 44 | 0.1424 | 0.3670 | | Postop Month 6 | Mesopic | (1.5) | 244 | 241 | 1 | 1.6016 | 0.2375 | 244 | 0 | 1.6725 | 0.2581 | 241 | 1 | 0.0712 | 0.1974 | | | | (3) | 244 | 241 | 1 | 1.6048 | 0.3484 | 244 | 0 | 1.6826 | 0.3950 | 241 | 1 | 0.0738 | 0.4925 | | | | (6) | 244 | 235 | 7 | 1.7003 | 0.2615 | 243 | 1 | 1.7962 | 0.2660 | 234 | 8 | 0.0990 | 0.2798 | | | | (12) | 244 | 206 | 36 | 1.3875 | 0.2911 | 226 | 18 | 1.4441 | 0.3051 | 198 | 44 | 0.0757 | 0.3306 | | | | (18) | 244 | 161 | 80 | 0.9893 | 0.2825 | 186 | 58 | 1.0592 | 0.3212 | 140 | 101 | 0.0871 | 0.3872 | | | Photopic | (1.5) | 244 | 235 | 0 | 1.5921 | 0.2372 | 244 | 0 | 1.6602 | 0.2488 | 235 | 0 | 0.0703 | 0.2178 | | | | (3) | 244 | 234 | 1 | 1.6257 | 0.3708 | 244 | 0 | 1.7204 | 0.4115 | 234 | 1 | 0.1016 | 0.5311 | | | | (6) | 244 | 234 | 1 | 1.8015 | 0.2542 | 244 | 0 | 1.9227 | 0.2385 | 234 | 1 | 0.1217 | 0.2510 | | | | (12) | 244 | 230 | 5 | 1.4720 | 0.2903 | 240 | 4 | 1.6186 | 0.2659 | 228 | 7 | 0.1440 | 0.2849 | | | | (18) | 244 | 201 | 33 | 1.0992 | 0.3064 | 234 | 10 | 1.2298 | 0.2924 | 198 | 36 | 0.1516 | 0.3395 | $^{1}$ *N$_{0}$ patients are not included in the mean because they could not see any contrast level. Mean results with N$_{0}$>0 are, therefore, biased upward; and, the corresponding standard deviations are biased downward. $^{2}$ Preop Mean: Calculated as the average of the log values of each individual preoperative contrast sensitivity measurement. $^{3}$ Postop Mean: Calculated as the average of the log values of each individual postoperative contrast sensitivity measurement. $^{4}$ Percent Change Mean: Calculated as the average of the individual paired differences (postop-preop) of the log values for each eye. {23} **Table 15: Changes in Log$_{10}$ Mesopic and Photopic Contrast Sensitivity (Log$_{10}$ [Threshold Contrast$^{-1}$]) With Glare at 3 Months and 6 Months after T-CAT LASIK$^{1}$** | Visit | Type | Cycles per Degree | Total N | Preop n | PreOp N_{0} | Preop Mean^{2} | Preop SD | Postop n | Visit N_{0} | Postop Mean^{3} | Postop SD | Paired Difference n | Difference N_{0} | Paired Difference Mean^{4} | Paired Difference SD | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Postop Month 3 | Mesopic | (1.5) | 247 | 242 | 4 | 1.5055 | 0.2758 | 244 | 1 | 1.5650 | 0.2703 | 239 | 5 | 0.0646 | 0.2269 | | | | (3) | 247 | 241 | 5 | 1.6835 | 0.2735 | 243 | 2 | 1.7323 | 0.2636 | 239 | 5 | 0.0502 | 0.2316 | | | | (6) | 247 | 229 | 16 | 1.6355 | 0.2964 | 241 | 4 | 1.7072 | 0.2577 | 226 | 18 | 0.0897 | 0.3025 | | | | (12) | 247 | 191 | 54 | 1.3714 | 0.3061 | 210 | 35 | 1.3590 | 0.2899 | 176 | 68 | 0.0178 | 0.3166 | | | | (18) | 247 | 146 | 99 | 1.0063 | 0.3021 | 168 | 77 | 0.9726 | 0.3013 | 119 | 125 | 0.0100 | 0.3791 | | | Photopic | (1.5) | 247 | 237 | 0 | 1.5689 | 0.2493 | 245 | 0 | 1.6574 | 0.2405 | 235 | 0 | 0.0935 | 0.2087 | | | | (3) | 247 | 235 | 2 | 1.7827 | 0.2229 | 245 | 0 | 1.8845 | 0.2151 | 233 | 2 | 0.1051 | 0.2022 | | | | (6) | 247 | 229 | 2 | 1.7926 | 0.2617 | 241 | 0 | 1.8936 | 0.2288 | 224 | 2 | 0.0999 | 0.2377 | | | | (12) | 247 | 223 | 14 | 1.4741 | 0.2853 | 242 | 3 | 1.5966 | 0.2663 | 220 | 16 | 0.1312 | 0.2911 | | | | (18) | 247 | 203 | 33 | 1.0776 | 0.2928 | 234 | 11 | 1.2248 | 0.2866 | 196 | 40 | 0.1619 | 0.3551 | | Postop Month 6 | Mesopic | (1.5) | 244 | 238 | 4 | 1.5004 | 0.2770 | 244 | 0 | 1.5809 | 0.2711 | 238 | 4 | 0.0838 | 0.2548 | | | | (3) | 244 | 237 | 5 | 1.6710 | 0.2642 | 242 | 2 | 1.7480 | 0.2847 | 236 | 6 | 0.0785 | 0.2789 | | | | (6) | 244 | 225 | 16 | 1.6228 | 0.2966 | 237 | 7 | 1.7281 | 0.2603 | 222 | 19 | 0.1053 | 0.3086 | | | | (12) | 244 | 185 | 56 | 1.3632 | 0.3001 | 219 | 25 | 1.3918 | 0.2989 | 177 | 64 | 0.0669 | 0.3138 | | | | (18) | 244 | 140 | 101 | 0.9968 | 0.2806 | 167 | 76 | 1.0124 | 0.2797 | 112 | 130 | 0.0374 | 0.3536 | | | Photopic | (1.5) | 244 | 235 | 0 | 1.5684 | 0.2502 | 244 | 0 | 1.6803 | 0.2562 | 235 | 0 | 0.1162 | 0.2405 | | | | (3) | 244 | 233 | 2 | 1.7905 | 0.2283 | 244 | 0 | 1.8821 | 0.2345 | 233 | 2 | 0.0918 | 0.2132 | | | | (6) | 244 | 227 | 2 | 1.7990 | 0.2572 | 243 | 1 | 1.9260 | 0.2428 | 226 | 3 | 0.1269 | 0.2646 | | | | (12) | 244 | 223 | 12 | 1.4746 | 0.2942 | 240 | 4 | 1.6296 | 0.2749 | 222 | 13 | 0.1610 | 0.3185 | | | | (18) | 244 | 203 | 31 | 1.0827 | 0.3105 | 231 | 13 | 1.2439 | 0.3152 | 195 | 39 | 0.1726 | 0.3688 | $^{1}$ *N$_{0}$ patients are not included in the mean because they could not see any contrast level. Mean results with N$_{0}$>0 are, therefore, biased upward; and, the corresponding standard deviations are biased downward. $^{2}$ Preop Mean: Calculated as the average of the log values of each individual preoperative contrast sensitivity measurement. $^{3}$ Postop Mean: Calculated as the average of the log values of each individual postoperative contrast sensitivity measurement. $^{4}$ Percent Change Mean: Calculated as the average of the individual paired differences (postop-preop) of the log values for each eye. PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 24 of 39 {24} ### Effectiveness Results A summary of key effectiveness variables at each of the postoperative visits is provided below in Table 16 for the myopia cohort treated with T-CAT LASIK. **Table 16: Summary of Key Effectiveness Parameters after T-CAT LASIK** | EFFECTIVENESS VARIABLES | | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | | --- | --- | --- | --- | --- | --- | --- | | MRSE +/- 0.50 D | n/N | 220/248 | 227/247 | 227/244 | 221/237 | 218/230 | | | (%) | (88.71%) | (91.90%) | (93.03%) | (93.25%) | (94.78%) | | | (CI) | ( 84.1, 92.4) | ( 87.8, 95.0) | ( 89.1, 95.9) | ( 89.3, 96.1) | ( 91.1, 97.3) | | MRSE +/- 1.00 D | n/N | 244/248 | 244/247 | 241/244 | 235/237 | 229/230 | | | (%) | (98.39%) | (98.79%) | (98.77%) | (99.16%) | (99.57%) | | | (CI) | ( 95.9, 99.6) | ( 96.5, 99.7) | ( 96.4, 99.7) | ( 97.0, 99.9) | ( 97.6,100.0) | | MRSE +/- 2.00 D | n/N | 248/248 | 247/247 | 243/244 | 237/237 | 230/230 | | | (%) | (100.0%) | (100.0%) | (99.59%) | (100.0%) | (100.0%) | | | (CI) | ( 98.5,100.0) | ( 98.5,100.0) | ( 97.7,100.0) | ( 98.5,100.0) | ( 98.4,100.0) | | UCVA 20/20 or better | n/N | 217/248 | 229/247 | 217/244 | 212/237 | 213/230 | | | (%) | (87.50%) | (92.71%) | (88.93%) | (89.45%) | (92.61%) | | | (CI) | ( 82.7, 91.3) | ( 88.7, 95.6) | ( 84.3, 92.6) | ( 84.8, 93.1) | ( 88.4, 95.6) | | UCVA 20/40 or better if BCVA 20/20 or better preop | n/N | 239/242 | 239/241 | 235/238 | 231/232 | 224/225 | | | (%) | (98.76%) | (99.17%) | (98.74%) | (99.57%) | (99.56%) | | | (CI) | ( 96.4, 99.7) | ( 97.0, 99.9) | ( 96.4, 99.7) | ( 97.6,100.0) | ( 97.5,100.0) | At all postoperative visits from 3 to 12 months, 89% or more of the eyes saw 20/20 or better without correction; and 92% or more of the eyes were within $\pm 0.5$ D of attempted MRSE. The key effectiveness parameters at 3 months after T-CAT LASIK, stratified by preoperative MRSE and by each preoperative cylinder, are presented below in Tables 17 and 18, respectively. Refractive stability is attained at 3 months postoperatively and confirmed at 6 months; thus, the 3-month time point of refractive stability visit was selected for presentation of these results. Similar clinical results are observed in the stratified bins at 3 months postoperatively as are seen in the entire cohort. Thus, the clinical effectiveness outcomes support the refractive range for the proposed indication for use. PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 25 of 39 {25} **Table 17: Summary of Key Effectiveness Parameters Stratified by Pre-Treatment MRSE – Results at 3 Months after T-CAT LASIK** | EFFECTIVENESS VARIABLES | | -0.01 TO -1.00D | -1.01 TO -2.00D | -2.01 TO -3.00D | -3.01 TO -4.00D | -4.01 TO -5.00D | -5.01 TO -6.00D | -6.01 TO -7.00D | -7.01 TO -8.00D | -8.01 TO -9.00D | CUM TOTAL | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | MRSE +/- 0.50 D | n/N | 8/ 8 | 36/ 37 | 37/ 40 | 32/ 33 | 24/ 28 | 25/ 26 | 18/ 20 | 26/ 29 | 21/ 26 | 227/247 | | | (%) | (100.0%) | (97.30%) | (92.50%) | (96.97%) | (85.71%) | (96.15%) | (90.00%) | (89.66%) | (80.77%) | (91.90%) | | | (CI) | (63.1,100.0) | (85.8, 99.9) | (79.6, 98.4) | (84.2, 99.9) | (67.3, 96.0) | (80.4, 99.9) | (68.3, 98.8) | (72.6, 97.8) | (60.6, 93.4) | (87.8, 95.0) | | MRSE +/- 1.00 D | n/N | 8/ 8 | 37/ 37 | 40/ 40 | 33/ 33 | 27/ 28 | 26/ 26 | 19/ 20 | 29/ 29 | 25/ 26 | 244/247 | | | (%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (96.43%) | (100.0%) | (95.00%) | (100.0%) | (96.15%) | (98.79%) | | | (CI) | (63.1,100.0) | (90.5,100.0) | (91.2,100.0) | (89.4,100.0) | (81.7, 99.9) | (86.8,100.0) | (75.1, 99.9) | (88.1,100.0) | (80.4, 99.9) | (96.5, 99.7) | | MRSE +/- 2.00 D | n/N | 8/ 8 | 37/ 37 | 40/ 40 | 33/ 33 | 28/ 28 | 26/ 26 | 20/ 20 | 29/ 29 | 26/ 26 | 247/247 | | | (%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | | | (CI) | (63.1,100.0) | (90.5,100.0) | (91.2,100.0) | (89.4,100.0) | (87.7,100.0) | (86.8,100.0) | (83.2,100.0) | (88.1,100.0) | (86.8,100.0) | (98.5,100.0) | | UCVA 20/20 or better | n/N | 8/ 8 | 36/ 37 | 36/ 40 | 32/ 33 | 26/ 28 | 24/ 26 | 16/ 20 | 27/ 29 | 24/ 26 | 229/247 | | | (%) | (100.0%) | (97.30%) | (90.00%) | (96.97%) | (92.86%) | (92.31%) | (80.00%) | (93.10%) | (92.31%) | (92.71%) | | | (CI) | (63.1,100.0) | (85.8, 99.9) | (76.3, 97.2) | (84.2, 99.9) | (76.5, 99.1) | (74.9, 99.1) | (56.3, 94.3) | (77.2, 99.2) | (74.9, 99.1) | (88.7, 95.6) | | UCVA 20/40 or better if BCVA 20/20 or better preop | n/N | 8/ 8 | 37/ 37 | 40/ 40 | 32/ 32 | 27/ 28 | 24/ 25 | 19/ 19 | 26/ 26 | 26/ 26 | 239/241 | | | (%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (96.43%) | (96.00%) | (100.0%) | (100.0%) | (100.0%) | (99.17%) | | | (CI) | (63.1,100.0) | (90.5,100.0) | (91.2,100.0) | (89.1,100.0) | (81.7, 99.9) | (79.6, 99.9) | (82.4,100.0) | (86.8,100.0) | (86.8,100.0) | (97.0, 99.9) | PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 26 of 39 {26} **Table 18: Summary of Key Effectiveness Parameters Stratified by Pre-Treatment Cylinder – Results at 3 Months after T-CAT LASIK** | EFFECTIVENESS VARIABLES | | 0.00D | 0.01 TO 0.50D | 0.51 TO 1.00D | 1.01 TO 2.00D | 2.01 TO 3.00D | 3.01 TO 4.00D | 4.01 TO 5.00D | 5.01 to 6.00D | CUM TOTAL | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | MRSE +/- 0.50 D | n/N | 33/ 37 | 66/ 72 | 43/ 45 | 40/ 43 | 27/ 29 | 11/ 12 | 5/ 7 | 2/ 2 | 227/247 | | | (%) | (89.19%) | (91.67%) | (95.56%) | (93.02%) | (93.10%) | (91.67%) | (71.43%) | (100.0%) | (91.90%) | | | (CI) | ( 74.6, 97.0) | ( 82.7, 96.9) | ( 84.9, 99.5) | ( 80.9, 98.5) | ( 77.2, 99.2) | ( 61.5, 99.8) | ( 29.0, 96.3) | ( 15.8,100.0) | ( 87.8, 95.0) | | MRSE +/- 1.00 D | n/N | 36/ 37 | 71/ 72 | 44/ 45 | 43/ 43 | 29/ 29 | 12/ 12 | 7/ 7 | 2/ 2 | 244/247 | | | (%) | (97.30%) | (98.61%) | (97.78%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (98.79%) | | | (CI) | ( 85.8, 99.9) | ( 92.5,100.0) | ( 88.2, 99.9) | ( 91.8,100.0) | ( 88.1,100.0) | ( 73.5,100.0) | ( 59.0,100.0) | ( 15.8,100.0) | ( 96.5, 99.7) | | MRSE +/- 2.00 D | n/N | 37/ 37 | 72/ 72 | 45/ 45 | 43/ 43 | 29/ 29 | 12/ 12 | 7/ 7 | 2/ 2 | 247/247 | | | (%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | | | (CI) | ( 90.5,100.0) | ( 95.0,100.0) | ( 92.1,100.0) | ( 91.8,100.0) | ( 88.1,100.0) | ( 73.5,100.0) | ( 59.0,100.0) | ( 15.8,100.0) | ( 98.5,100.0) | | UCVA 20/20 or better | n/N | 36/ 37 | 67/ 72 | 44/ 45 | 42/ 43 | 25/ 29 | 9/ 12 | 4/ 7 | 2/ 2 | 229/247 | | | (%) | (97.30%) | (93.06%) | (97.78%) | (97.67%) | (86.21%) | (75.00%) | (57.14%) | (100.0%) | (92.71%) | | | (CI) | ( 85.8, 99.9) | ( 84.5, 97.7) | ( 88.2, 99.9) | ( 87.7, 99.9) | ( 68.3, 96.1) | ( 42.8, 94.5) | ( 18.4, 90.1) | ( 15.8,100.0) | ( 88.7, 95.6) | | UCVA 20/40 or better if BCVA 20/20 or better preop | n/N | 37/ 37 | 69/ 70 | 45/ 45 | 42/ 42 | 28/ 28 | 10/ 10 | 6/ 7 | 2/ 2 | 239/241 | | | (%) | (100.0%) | (98.57%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (85.71%) | (100.0%) | (99.17%) | | | (CI) | ( 90.5,100.0) | ( 92.3,100.0) | ( 92.1,100.0) | ( 91.6,100.0) | ( 87.7,100.0) | ( 69.2,100.0) | ( 42.1, 99.6) | ( 15.8,100.0) | ( 97.0, 99.9) | PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 27 of 39 {27} In the stratified MRSE and stratified cylinder analyses, at least 90.0% of the eyes in each dioptric group (except the highest MRSE -8.01 to -9.00 D, MRSE -4.00 to -5.00, and 4.01 to 5.00 D cylinder groups) achieved a postoperative refraction that was within $\pm 0.5$ D of the attempted refraction. This closely approximates the results for the entire cohort, in which 91.9% of all T-CAT LASIK treated eyes were within $\pm 0.5$ D of the attempted achieved manifest refraction. #### Stability of Refractive Outcome Refractive stability was calculated as the mean change (paired differences) in MRSE ($\pm S.D.$ and 95% C.I.) between pairs of successive refractions. Refractive stability for eyes that completed one or more pairs of successive postoperative visits is presented below in Table 19 for a consistent cohort of 227 eyes that completed every postoperative visit at 1, 3, 6, 9, and 12 months. As shown in Table 19 the mean annual change in MRSE from 1 to 3 months and from 3 to 6 months was -0.050 D/year and -0.176 D/year, respectively, for the consistent cohort of eyes. The mean change is well below the target value of 0.5 D/year change in MRSE. Additionally, 99.6% of the eyes in the consistent cohort had a change in MRSE from 1 to 3 months that was $\leq 1.0$ D; and 100% of the eyes achieved this same degree of refractive stability for the 3 to 6 month postoperative interval. Based on these analyses, refractive stability is achieved at 3 months and confirmed at 6 months postoperatively for this cohort of eyes treated with T-CAT LASIK. **Table 19: Refractive Stability for Eyes that Have Paired Differences at All of the Specified Visit Intervals (Completed All Visits) – All Eyes Treated** | Stability Criterion | | Week 1 to Month 1 | Month 1 to Month 3 | Month 3 to Month 6 | Month 6 to Month 9 | Month 9 to Month 12 | | --- | --- | --- | --- | --- | --- | --- | | Change of MRSE <= 1.0 D | n/N | 227/227 | 226/227 | 227/227 | 227/227 | 226/227 | | | (%) | (100.0%) | (99.56%) | (100.0%) | (100.0%) | (99.56%) | | | (CI) | ( 98.4,100.0) | ( 97.6,100.0) | ( 98.4,100.0) | ( 98.4,100.0) | ( 97.6,100.0) | | Change of MRSE <= 0.5 D | n/N | 212/227 | 217/227 | 219/227 | 216/227 | 218/227 | | | (%) | (93.39%) | (95.59%) | (96.48%) | (95.15%) | (96.04%) | | | (CI) | ( 89.3, 96.3) | ( 92.0, 97.9) | ( 93.2, 98.5) | ( 91.5, 97.6) | ( 92.6, 98.2) | | Change of MRSE in diopters | Mean | 0.058 | -0.008 | -0.044 | -0.017 | 0.014 | | | Std | 0.09 | 0.07 | 0.06 | 0.06 | 0.06 | | | (CI) | ( 0.02, 0.10) | (-0.04, 0.03) | (-0.08,-0.01) | (-0.05, 0.01) | (-0.02, 0.05) | | Mean Change of MRSE per Year | Mean | 0.694 | -0.050 | -0.176 | -0.068 | 0.057 | | | Std | 13.40 | 2.66 | 1.04 | 0.89 | 1.00 | | | (CI) | ( 0.22, 1.17) | (-0.26, 0.16) | (-0.31,-0.04) | (-0.19, 0.06) | (-0.07, 0.19) | #### Manifest Sphere and Manifest Cylinder Descriptive Statistics Descriptive statistics for manifest sphere and manifest cylinder for each study visit are summarized below in Tables 20 and 21, respectively. Descriptive statistics for MRSE at screening through 12 months after T-CAT LASIK are summarized in Table 22. As shown in the tables below, the T-CAT LASIK procedure achieves good accuracy for all three parameters. At 3 months postoperatively, the mean PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 28 {28} sphere, cylinder, and MRSE are 0.15 D ($\pm 0.37$), -0.19 D ($\pm 0.32$), and 0.06 D ($\pm 0.33$), respectively. The standard deviations of approximately 0.33 D for each parameter are well within the accepted standards for variability of these manifest refraction measurements. The mean sphere, cylinder, and MRSE change very little over time from 3 months to 12 months, with the mean sphere and MRSE decreasing slightly to 0.09 D and 0.00 D, respectively, and the mean cylinder remaining unchanged at -0.19 D. **Table 20: Descriptive Statistics for Manifest Refraction Sphere** | Visit | n | Mean Sphere | Standard Deviation | Lower 95% Confidence Limit | Upper 95% Confidence Limit | | --- | --- | --- | --- | --- | --- | | Screening | 249 | -4.01 | 2.57 | -4.33 | -3.69 | | Postop Month 1 | 248 | 0.18 | 0.39 | 0.13 | 0.22 | | Postop Month 3 | 247 | 0.15 | 0.37 | 0.11 | 0.20 | | Postop Month 6 | 244 | 0.11 | 0.37 | 0.06 | 0.16 | | Postop Month 9 | 237 | 0.09 | 0.34 | 0.04 | 0.13 | | Postop Month 12 | 230 | 0.09 | 0.33 | 0.05 | 0.14 | **Table 21: Descriptive Statistics for Manifest Refraction Cylinder** | Visit | n | Mean Cylinder | Standard Deviation | Lower 95% Confidence Limit | Upper 95% Confidence Limit | | --- | --- | --- | --- | --- | --- | | Screening | 249 | -1.19 | 1.23 | -1.34 | -1.04 | | Postop Month 1 | 248 | -0.22 | 0.33 | -0.26 | -0.18 | | Postop Month 3 | 247 | -0.19 | 0.32 | -0.23 | -0.15 | | Postop Month 6 | 244 | -0.19 | 0.30 | -0.23 | -0.15 | | Postop Month 9 | 237 | -0.19 | 0.30 | -0.22 | -0.15 | | Postop Month 12 | 230 | -0.19 | 0.30 | -0.23 | -0.15 | **Table 22: Descriptive Statistics for Manifest Refraction Sphere Equivalent (MRSE)** | Visit | n | Mean MRSE | Standard Deviation | Lower 95% Confidence Limit | Upper 95% Confidence Limit | | --- | --- | --- | --- | --- | --- | | Screening | 249 | -4.61 | 2.43 | -4.91 | -4.30 | | Postop Month 1 | 248 | 0.06 | 0.36 | 0.02 | 0.11 | | Postop Month 3 | 247 | 0.06 | 0.33 | 0.01 | 0.10 | | Postop Month 6 | 244 | 0.01 | 0.35 | -0.03 | 0.06 | | Postop Month 9 | 237 | -0.01 | 0.30 | -0.04 | 0.03 | | Postop Month 12 | 230 | -0.00 | 0.27 | -0.04 | 0.04 | PMA P020050/S12: FDA Summary of Safety and Effectiveness Data Page 29 {29} ### Uncorrected Visual Acuity Table 23 below shows that nearly one-third of the eyes treated for myopia with T-CAT LASIK (78/247, 31.6%) achieved a distance UCVA of 20/12.5 or better, and over two-thirds of the eyes (170/247; 68.9%) were seeing 20/16 or better without correction at 3 months postoperatively. Furthermore, a total of 93% of the T-CAT LASIK eyes had a UCVA of 20/20 or better at 3 and 12 months postoperatively, with slight shifts toward continuing improvement in the proportion of these eyes that attained UCVA of 20/16, 20/12.5, and 20/10 through 12 months after T-CAT LASIK. **Table 23: Summary of Changes in Uncorrected Visual Acuity** | UCVA Criterion | | Preop | Month 1 | Month 3 | Month 6 | Month 9 | Month 12 | | --- | --- | --- | --- | --- | --- | --- | --- | | 20/10 or better | n/N | 0/249 | 11/248 | 19/247 | 25/244 | 30/237 | 36/230 | | | (%) | ( 0.00%) | ( 4.44%) | ( 7.69%) | (10.25%) | (12.66%) | (15.65%) | | 20/12.5 or better | n/N | 0/249 | 59/248 | 78/247 | 69/244 | 72/237 | 79/230 | | | (%) | ( 0.00%) | (23.79%) | (31.58%) | (28.28%) | (30.38%) | (34.35%) | | 20/16 or better | n/N | 0/249 | 146/248 | 170/247 | 172/244 | 152/237 | 149/230 | | | (%) | ( 0.00%) | (58.87%) | (68.83%) | (70.49%) | (64.14%) | (64.78%) | | 20/20 or better | n/N | 0/249 | 217/248 | 229/247 | 217/244 | 212/237 | 213/230 | | | (%) | ( 0.00%) | (87.50%) | (92.71%) | (88.93%) | (89.45%) | (92.61%) | | 20/25 or better | n/N | 4/249 | 240/248 | 240/247 | 235/244 | 231/237 | 222/230 | | | (%) | ( 1.61%) | (96.77%) | (97.17%) | (96.31%) | (97.47%) | (96.52%) | | 20/32 or better | n/N | 7/249 | 244/248 | 244/247 | 241/244 | 234/237 | 227/230 | | | (%) | ( 2.81%) | (98.39%) | (98.79%) | (98.77%) | (98.73%) | (98.70%) | | 20/40 or better | n/N | 11/249 | 245/248 | 245/247 | 241/244 | 236/237 | 229/230 | | | (%) | ( 4.42%) | (98.79%) | (99.19%) | (98.77%) | (99.58%) | (99.57%) | | 20/50 or better | n/N | 19/249 | 246/248 | 247/247 | 242/244 | 236/237 | 229/230 | | | (%) | ( 7.63%) | (99.19%) | (100.0%) | (99.18%) | (99.58%) | (99.57%) | | 20/63 or better | n/N | 34/249 | 247/248 | 247/247 | 243/244 | 236/237 | 230/230 | | | (%) | (13.65%) | (99.60%) | (100.0%) | (99.59%) | (99.58%) | (100.0%) | | 20/80 or better | n/N | 42/249 | 247/248 | 247/247 | 244/244 | 237/237 | 230/230 | | | (%) | (16.87%) | (99.60%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | | 20/100 or better | n/N | 54/249 | 247/248 | 247/247 | 244/244 | 237/237 | 230/230 | | | (%) | (21.69%) | (99.60%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | | 20/125 or better | n/N | 64/249 | 247/248 | 247/247 | 244/244 | 237/237 | 230/230 | | | (%) | (25.70%) | (99.60%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | | 20/160 or better | n/N | 79/249 | 248/248 | 247/247 | 244/244 | 237/237 | 230/230 | | | (%) | (31.73%) | (100.…