NIDEK EC-5000 EXCIMER LASER SYSTEM

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA # 1. GENERAL INFORMATION | Device Generic Name: | Ophthalmic Excimer Laser System | | --- | --- | | Device Trade Name: | Nidek EC-5000 Excimer Laser System | | Applicant's Name and Address: | Nidek Co. LTD 34-14 Maehama Hiroishi-cho Gamagori, Aichi Japan | U.S. Office: Nidek, Inc. 47651 Westinghouse Drive Fremont, California 94539 Date of Panel Recommendation: None Premarket Approval (PMA) Application Number: P970053/S9 Date of Notice of Approval to Applicant: October 11, 2006 The Nidek EC-5000 Excimer Laser System was originally approved on December 17, 1998 under PMA P970053 for the limited indication for myopic photorefractive keratectomy (PRK) uncomplicated by astigmatism (≤ -0.75 D) in patients 21 years of age or older with -0.75 to -13.0 D of myopia whose refractive change for one year prior to treatment is within ±0.5 D for low myopia (≤ -7.0 D MRSE) or within ± 1.0 D for high myopia (> -7.0 D MRSE). The clinical indication was expanded in Supplement 1 (approved September 29, 1999) to include PRK treatment of myopic astigmatism (-1.00 to -8.00 D MRSE with -0.5 to -4.00 D cylinder). Supplement 6 (approved September 4, 2001) further expanded the clinical indication to include laser assisted in-situ keratomilicusis (LASIK) for the treatment of myopic astigmatism (-1.00 to -14.00 D MRSE with up to -4.00 D astigmatism) using an optical zone between 5.0 and 6.5 mm in patients 21 years of age or older. Supplements 7 and 8 added the use of active eye trackers operating at 60 Hz and 200 Hz, respectively, for the approved myopic and myopic astigmatism indications. The sponsor submitted this supplement to further expand the clinical indications. The updated clinical data to support the expanded indication is provided in this summary. The hazard analysis, software testing, preclinical test results, and profilometry validation of P970053/S009 SSED Page 1 of 36 8 {1} ablation patterns for spherical hyperopia and hyperopic astigmatism supporting this indication were submitted in this supplement. Refer to the SSED of the original PMA (P970053) for information on non-clinical studies that were previously performed for the EC-5000 Excimer Laser System that did not need to be repeated for the hyperopia indication. Written requests for copies of the SSED can be obtained from the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20857 under Docket # 00M-1640 (P970053), Docket # 00M-1664 (S1), and Docket 01M-0014 (S2) or you may download the files from the internet site: http://www.fda.gov/cdrh/pdf/p970053.html # II. INDICATIONS FOR USE The Nidek EC-5000 Excimer Laser System is indicated for Laser-Assisted In-Situ Keratomileusis (LASIK) treatment: - for the reduction or elimination of hyperopia refractive errors from \(+0.5\) to \(+5.0\) D of sphere with or without astigmatic refractive errors from \(+0.5\) to \(+2.0\) D at the spectacle plane with manifest refraction spherical equivalent (MRSE) of \(+5.0\) D or less; in patients 21 years of age or older; and, - in patients with documented stability of manifest refraction over the prior year, demonstrated by a change in manifest refraction spherical equivalent (MRSE) not greater than \(\pm 0.5\) D. # III. CONTRAINDICATIONS LASIK surgery is contraindicated in: Patients with collagen vascular, autoimmune or immunodeficiency diseases; - Pregnant or nursing women; - Patients with signs of keratoconus, keratoconus suspect, or unstable central keratometry readings with irregular mires; - Patients who are taking one or both of the following medications: isotretinoin (Accutane®) or amiodarone hydrochloride (Cordaron®); or, - Eyes that have a calculated residual stromal bed thickness that is less than 250 microns. To avoid corneal ectasia, residual corneal bed thickness remaining after laser ablation must be calculated preoperatively to be 250 microns or greater. P970053/S009 SSED Page 2 of 36 9 {2} # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the device labeling. # V. DEVICE DESCRIPTION # A. Microkeratome The LASIK procedure required the use of a commercially available microkeratome that has been cleared for marketing via premarket notification. Three different microkeratomes and one femtosecond laser were used in this study. Each microkeratome consisted of a sterilization/storage tray, which includes the shaper head, a left/right eye adapter, suction ring, suction handle, blade handling pin, and corneal reference marker. The instrument motor, tonometer, cleaning brush, disposable blades, power/suction supply unit with vacuum and motor footswitches, and power cords are provided as separate components in an accessory stand and equipment suitcase which complete the system. Microkeratomes used in the clinical study included: MK-2000 (Nidek Co., LTD; Gamagori, Japan), Moria M2 (Moria USA; Doylestown, PA), and Hansatome (Bausch & Lomb; Rochester, NY). The femtosecond laser used in the clinical study was an IntraLase FS (IntraLase Corporation; Irvine, CA). # B. Nidek EC-5000 Excimer Laser System The Nidek EC-5000 Excimer Laser System is an ophthalmic laser system for refractive surgery of the cornea designed to correct the vision of subjects with a variety of refractive errors (myopia, myopic astigmatism, hyperopia, and hyperopic astigmatism). The Nidek EC-5000 device consists of an argon fluoride (ArF) excimer laser and beam delivery system, a diode aiming laser; the laser optical viewing system including the microscope, fixation light, and illumination lamps; the mechanical systems used for positioning, focusing, and gas handling; and microprocessor controllers. The Nidek EC-5000 Excimer Laser System uses a 193 nm ArF laser beam to recontour the cornea by ablation of corneal tissue. The laser system features a scanning beam delivery system in which the laser beam is dynamically rotated about the optical axis and paired with an iris diaphragm in a series of predetermined beam offset positions to produce a series of circular scan patterns for hyperopic corrections, eliminating the need for the slit aperture that is used for myopic ablations. The hyperopic treatment is a time-based treatment in which the degree of refractive treatment applied is mathematically calculated to determine the amount of time the scanning beam must spend in each beam offset position to produce the desired hyperopic treatment shape. The treatment algorithm and laser P970053/S009 SSED Page 3 of 36 10 {3} treatment parameters were empirically optimized based on international clinical results. For hyperopia spherical corrections, the optical axis of the system is first aligned with the optical axis of the cornea. Then, the linear scanning mirror is set at a fixed position relative to the optical axis of the cornea, thereby establishing an offset for the laser beam. This offset is later increased in steps throughout the treatment, beginning with step 1 and ending with step 7. Pulses are delivered such that they are positioned 159 degrees apart and overlap by 21 degrees. After the first step is completed, the linear scanning mirror is moved to the second step. The iris diaphragm continues to open at a specified rate and the laser beam continues to rotate about the corneal axis and fire at the same constant rate as in Step 1. This sequence of events is completed for each of the seven steps. For cylindrical corrections, the laser scanning method is the same as spherical corrections, except that the angular separation of each pulse is 180 degrees rather than 159 degree angular separation used for spherical corrections. The laser parameters used in the clinical study were as follows: | Model | EC-5000 (Model EC2B) | | --- | --- | | Pulse Repetition Rate | 34 Hz | | Fluence (nominal) | 300 mJ/cm²/scan (mean at the cornea) | | Slit Beam | 2 mm by 10 mm (FWHM) | | Iris Diaphragm Diameter | 10 mm (Max) | | Optical Zone | 6.0 mm | | Ablation Zone | 9.0 mm | | Ablation Rate in Cornea | 0.6 μm/scan | | Ablation Rate in PMMA | 0.315 μm/scan | | PMMA/Cornea Ratio | 0.89 | | Cyl/Sph Ratio | 0.32 | The software versions in the laser system used during the clinical trial were: | Laser Operating System | Windows 2000 v.5.26(a) | | --- | --- | | 200 Hz Eye tracker | ETC v.4.10 | | Dragon Eye Software | v.3.15 | The software versions in the laser system at approval are: | Laser Operating System | Windows 2000 v.5.27 | | --- | --- | | 200 Hz Eye tracker | ETC v.4.10 | | Dragon Eye Software | v.3.20 | P970053/S009 SSFD Page 4 of 36 11 {4} The Nidek EC-5000 Excimer Laser System for hyperopia plus astigmatism ablations is locked out for spherical treatments greater than +5.00 D, cylindrical treatments greater than +2.00 D cylinder, for treatments with an MRSE greater than +5.0 D, and for optical zones (OZ) different from the approved OZ of 6.0 mm or treatment zones (TZ) different from the approved TZ of 9.0 mm. The systems of the EC-5000 Excimer Laser used in the hyperopia clinical study include: 1. Optical Transmission System The optical delivery system aims to deliver the laser beam oscillated from the laser head and coaxial aiming beam to the cornea. The optical delivery system consists of mirrors, attenuator controller, laser shutter, linear scanning and image control, astigmatic control unit, variable circular iris diaphragm that controls the size, shape, and position of the laser beam, aiming shutter and projection lens. The linear scanning mechanism is driven by a stepping motor and a cylinder cam feed followed by an image rotator mechanism which is also driven by a stepping motor. Both mechanisms are equipped with sensors and encoders for positional feedback. 2. Energy Monitoring and Control The beam fluence is monitored directly by monitoring the energy of the laser beam. An energy detector, placed in the laser head, is used to monitor the energy and will shut off the laser beam if the fluence is too high or too low. It is recommended that the surgeon perform a calibration before each surgery. 3. Gas Handling System The EC-5000 Excimer Laser System incorporates two gas supply devices. The premix ArF gas is used for laser light formation and the nitrogen gas is used to rinse the beam path and optics during treatment. 4. Eye Tracking System The Eye Tracking System is used to measure eye movements from a digital high speed video camera at a sampling rate of 200 Hz, with a sampling interval of 5.0 ms. The eye position data are used to control the scanner position of the laser and validity flags are used to control the actual firing of the laser. The active video eye tracker can be decentered by the operator. P970053/S009 SSED Page 5 of 36 12 {5} # 5. Operating Microscope The observation system consists of an operational microscope. Observation and alignment of the cornea are performed through the operation microscope. Observation of the cornea is always possible even before, after, and during laser emission. # 6. Fixation Target The fixation lamp is positioned on the same path as the path of the excimer laser beam to make the patient's visual line coaxial with the optical path of the laser. # 7. Alignment and Illumination System The alignment and illumination system consists of alignment illumination (inner illumination which is also used for alignment), external illumination, an arm control system that varies exposure and focusing position, and the fixation lamp. The correct eye exposure position is identified by the use of the aiming beam, which is coaxial to the excimer laser as viewed through the operational microscope. The focusing position occurs when the reflection of the optical alignment illumination lights, which shine on the cornea in two different directions, are superimposed on each other. The initial exposure position is aligned to the center of the pupil and the focusing position is aligned to the surface of the cornea by the motorized control stick and the focusing knob. When the eye tracker is activated, it automatically tracks the center of the patient pupil; it is not necessary to perform subsequent alignment with the control stick. # 8. Patient Bed The patient lays on his/her back on the movable and height adjustable bed, which enables the operator to position and center the patient under the laser beam. # 9. Laser System Software Control The Windows 2000 based laser control software contains a hyperopic module that controls the hyperopic and hyperopic astigmatism ablation patterns. The hyperopic treatment module is security key controlled. # VI. ALTERNATIVE PRACTICES AND PROCEDURES Alternative methods of correcting farsightedness (hyperopia) with and without astigmatism include: glasses, contact lenses, photorefractive keratectomy (PRK), LASIK, conductive keratoplasty (CK), and Laser Thermal Keratoplasty (LTK). P970053/S009 SSED Page 6 of 36 13 {6} # VII. MARKETING HISTORY The EC-5000 Excimer Laser System has been distributed worldwide in more than 50 countries including Algeria, Argentina, Australia, Bahrain, Belgium, Bolivia, Brazil, Canada, Chile, China, Costa Rica, Croatia, Czech Republic, Dominican Republic, Ecuador, Egypt, Finland, France, Germany, Greece, India, Indonesia, Iran, Ireland, Israel, Italy, Korea, Kuwait, Japan, Jordan, Lebanon, Malaysia, Mexico, New Zealand, Oman, Norway, Pakistan, Paraguay, Peru, Poland, Puerto Rico, Romania, Russia, Saudi Arabia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Syria, Taiwan, Thailand, Tunisia, Turkey, UAE, UK, Ukraine, United States, Uruguay, and Venezuela. The Nidek EC-5000 Excimer Laser System has not been withdrawn from any country or market for reasons of safety or effectiveness. # VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Potential adverse effects associated with LASIK include: loss of best spectacle-corrected visual acuity (BSCVA), double vision, sensitivity to bright lights, difficulty with night vision, fluctuations in vision, increased intraocular pressure, corneal haze, secondary surgical intervention, corneal infiltrate or ulcer, corneal epithelial defect, corneal edema, problems associated with the flap including a lost, misplaced, or misaligned flap, and retinal vascular accidents. Please refer to complete listing of adverse events and complications observed during the clinical study, which are presented in tables 28 and 29 of the Summary of Clinical Studies, Section X. # IX. SUMMARY OF PRECLINICAL STUDIES A. Nidek EC-5000 Excimer Laser System 1. Hazard Analysis and Software Validation Hazard analysis and software validation testing were conducted for the Nidek EC-5000 Excimer Laser System hyperopic treatment module and the Windows-based sytem operating software. The hazard analysis includes risk assessment of hazards to the patient, operator, service personnel, bystanders, manufacturing personnel, and the environment. The software validation procedures covered all aspects of new software specifications and design, development, testing, functionality and performance. The hazard analysis and software validation testing indicated no new hazards affecting safety or effectiveness. Refer to the EC-5000 Excimer Laser System Operator's Manual and the Hyperopia Operator's Manual for safety precautions for the use of the excimer laser system. P970053/S009 SSED Page 7 of 36 14 {7} # 2. Profilometry of Ablation As a part of this PMA, Nidek validated the accuracy of the hyperopic astigmatic corrections by performing a variety of test ablations on flat and curved plastic surfaces. The degree of decreased ablation efficiency associated with the change in peripheral corneal curvature was evaluated using flat plastic surfaces tilted at angles to correspond to corneal curvature. All ablations were scanned with a surface profilometer and showed good agreement to theoretical targets. # X. SUMMARY OF CLINICAL STUDIES A clinical study of LASIK treatment with the Nidek EC-5000 Excimer Laser System for the correction of hyperopia with and without astigmatism was conducted under IDE G030204. Specifically, safety and effectiveness outcomes at 6 months postoperatively were assessed, as refractive stability is reached by that time. The IDE study is described in detail as follows: # A. Study Objective The objective of this clinical study was to demonstrate that LASIK treatment with the Nidek EC-5000 is safe and effective for the correction of hyperopia with and without astigmatism. # B. Study Design This was a prospective, non-randomized, open-label, multi-center study in which the control was the preoperative state of the treated eye (i.e., comparison of pretreatment and post-treatment visual parameters in the same eye). # C. Inclusion and Exclusion Criteria Enrollment in the study on the effect of LASIK treatment with the Nidek EC-5000 Excimer Laser System was limited to those subjects who met the following inclusion and exclusion criteria: - 21 years of age or older; - Had an uncorrected refractive error that could be surgically treated by LASIK consisting of spherical hyperopia (+0.5 D to +6.0 D and untreated cylinder less than +0.50 D) or hyperopic astigmatism with a spherical component of +0.5 D to +6.0 D, and an astigmatic component of +0.50 D to +3.0 D), based on the manifest refraction in the operative study eye; P970053/S009 SSED Page 8 of 36 15 {8} - Target postoperative refraction of 0.00 D sphere and 0.00 D cylinder (eyes treated for hyperopic astigmatism) or 0.00 D MRSE (eyes treated for spherical hyperopia) in the operative study eye; - BSCVA distance of 20/25 or better in each eye; - Less than 0.75 D SE difference between the screening cycloplegic and screening manifest refractions; - A stable correction (± 0.5 D) in the operative study eye, as determined by MRSE for a minimum of 12 months prior to surgery; - For contact lens wearers, demonstration of a stable refraction (± 0.5 D MRSE) of the manifest refraction and topography on two consecutive exam dates at least 7 days apart after discontinuation of contact lens wear; - Normal topography; - Signed written informed consent; and, - Willingness and ability to comply with schedule for follow-up visits. Subjects were not permitted to enroll in the study if they met any of the following exclusion criteria: - An acute or chronic disease or illness that would increase the operative risk or confound the outcome(s) of the study (e.g., severe dry eyes, immunocompromised, connective tissue disease with ocular involvement, clinically significant atopic disease, diabetes with ocular involvement, etc.); - Use of systemic medications that may confound the outcome of the study or increase the risk to the subject, including, but not limited to steroids, antimetabolites, etc.; - Previous ocular condition (other than refractive error) that may predispose the eye for future complications, for example: history of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome or corneal dystrophy, etc.); - Evidence of retinal vascular disease; - Keratoconus or unstable central keratometry readings with irregular mires; - Glaucoma or glaucoma suspect by exam findings; - Previous intraocular or corneal surgery, except strabismus surgery; - Pregnancy or lactation during the course of the study; - A known sensitivity to study medications; - Mixed astigmatism in the operative study eye, based on the screening manifest refraction; P970053/S009 SSED Page 9 of 36 16 {9} - Surgical treatment plan in the study eye(s) for monovision or intentional undercorrection or overcorrection; - Residual corneal bed thickness remaining after laser ablation is calculated preoperatively to be less than 250 microns in the operative study eye; - Preoperative central corneal thickness of less than 475 microns in the operative study eye; - Concurrent participation in other ophthalmic clinical trials; - Contact lens intolerance in subjects who are not undergoing bilateral treatment; or, - Mesopic pupil size ≥ 8mm. # D. Study Plan, Patient Assessments, and Outcome Evaluations - Subjects completed follow-up examinations at 1 day, 1 week, and 1, 3, 6, 9, and 12 months post-LASIK. - Subjects were permitted to have second eyes (fellow eyes) treated at the discretion of the investigator at the same time as the first eyes (primary eyes) or after the primary eye treatment. - Subjects were ineligible for retreatment unless specific permission was obtained from the sponsor, FDA, and the IRB. - All study treatments were conducted using a 6 mm diameter optical zone and 9 mm diameter ablation zone with intention of full correction to emmetropia. - Parameters measured during the study were: slit lamp examination of the eye, corneal topography, cycloplegic refraction, manifest refraction, UCVA distance and near, BSCVA distance and near, pupil size measurements, dilated fundus examination, keratometry, pachymetry, and intraocular pressure measurements. Safety monitoring throughout the study included observations at appropriate times for complications, adverse events, and clinically significant findings on ophthalmic examination. Subjective complaints were evaluated by means of a patient questionnaire. The primary efficacy variables for this study were improvement of UCVA, predictability of manifest refraction spherical equivalent (MRSE), and refractive stability. No retreatments were performed in the study. P970053/S009 SSED Page 10 of 36 17 {10} # E. Study Period, Investigational Sites, and Demographic Data # 1. Study Period A total of 293 eyes in 148 subjects were treated between December 10, 2003 and December 2, 2004. The database for this PMA supplement reflected data collected through March 1, 2006 and included 293 eyes: 144 spherical hyperopia eyes and 149 hyperopic astigmatism eyes. There were 6 investigational sites in the U.S. and 1 investigational site in Mexico that provided eligible data for analysis. # 2. Demographics Of the 148 subjects enrolled in the study, 32% (48/148) were male and 68% (100/148) were female. Racial distribution consisted of 70% Caucasian (103/148); 28% Hispanic (42/148); 1% Black (2/148); and, 1% Asian (1/148). The cohort had a mean age of 49.5 years with a range of 23 to 69 years. Table 1 presents demographic information for the cohort of subjects enrolled in the study. | TABLE 1 Subject Population Demographic Characteristics | | | | --- | --- | --- | | GENDER | N | % (N=148) | | Male | 48 | 32 | | Female | 100 | 68 | | RACE | | | | Caucasian | 103 | 70 | | Black | 2 | 1 | | Asian | 1 | 1 | | Hispanic | 42 | 28 | | AGE (YR) | N | 148 | | | Mean | 49.54 | | | Std | 8.88 | | | Min | 23 | | | Max | 69 | P970053/S009 SSED Page 11 of 36 18 {11} # F. Data Analysis and Results # 1. Baseline Characteristics The preoperative refractive errors for the entire cohort of treated eyes are summarized in Table 2 (stratified by baseline sphere and cylinder) and Table 3 (stratified by baseline MRSE) below. | TABLE 2 Preoperative Refractive Errors Stratified by Baseline Sphere and Cylinder | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Sphere | Cylinder | | | | Total Hyperopic Astigmatism | TOTAL EYES ENROLLED | | | 0 - 0.49 | 0.50 - 1.00 | 1.01 - 2.00 | 2.01 - 3.00 | | | | 0.5 - 1.00 | 3 | 13 | 4 | 3 | 20 | 23 | | 1.01 - 2.00 | 58 | 34 | 12 | 0 | 46 | 104 | | 2.01 - 3.00 | 44 | 33 | 9 | 2 | 44 | 88 | | 3.01 - 4.00 | 29 | 12 | 8 | 3 | 23 | 52 | | 4.01 - 5.00 | 8 | 5 | 4 | 1 | 10 | 18 | | 5.01 - 6.00 | 2 | 4 | 1 | 1 | 6 | 8 | | Total Treated | 144 | 101 | 38 | 10 | 149 | 293 | | | Spherical Hyperopia Eyes | Hyperopic Astigmatism Eyes | | | | TOTAL | | TABLE 3 Preoperative Refractive Errors Stratified by Baseline Manifest Refraction Spherical Equivalent (MRSE) | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | MRSE | Cylinder | | | | Total Hyperopic Astigmatism | TOTAL EYES ENROLLED | | | 0 - 0.49 | 0.50 - 1.00 | 1.01 - 2.00 | 2.01 - 3.00 | | | | 0.5 - 1.00 | 3 | 7 | 0 | 0 | 7 | 10 | | 1.01 - 2.00 | 57 | 30 | 9 | 1 | 40 | 97 | | 2.01 - 3.00 | 45 | 35 | 11 | 2 | 48 | 93 | | 3.01 - 4.00 | 29 | 19 | 10 | 0 | 29 | 58 | | 4.01 - 5.00 | 8 | 3 | 4 | 5 | 12 | 20 | | 5.01 - 6.00 | 2 | 6 | 3 | 1 | 10 | 12 | | > 6.00 | 0 | 1 | 1 | 1 | 3 | 3 | | Total Treated | 144 | 101 | 38 | 10 | 149 | 293 | | | Spherical Hyperopia Eyes | Hyperopic Astigmatism Eyes | | | | TOTAL | P970053/S009 SSED Page 12 of 36 19 {12} # 2. Postoperative Characteristics and Results # a. Accountability Accountability by eye for the 293-eye cohort is summarized in Table 4 below for the entire cohort of treated eyes. Accountability was calculated using the following formula: $$\% \text{ Accountability} = \frac{\text{Available for Analysis}}{\text{Enrolled} - \text{Discontinued} - \text{Not Yet Eligible}} \times 100$$ Overall accountability was greater than 99% at all visits through 6 months, with more than 99% of the cohort available for inclusion in the data analysis for determination of refractive stability at 6 months and 98% of the eyes available for confirmation of refractive stability at the 9-month examination. | TABLE 4 Accountability | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Status | 1 Day | | 1 WK | | 1 MO | | 3 MO | | 6 MO | | 9 MO | | 12 MO | | | Enrolled (N) | 293 | | 293 | | 293 | | 293 | | 293 | | 293 | | 293 | | | | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | n/N | % | | Available for Analysis | 293 | 100.0 | 293 | 100.0 | 291 | 99.3 | 291 | 99.3 | 291 | 99.3 | 287 | 98.0 | 279 | 95.2 | | Discontinued (Retreated) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Active (Not Eligible for Interval) | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | Lost to Follow-up | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 2 | 0.7 | 2 | 0.7 | 2 | 0.7 | 2 | 0.7 | | Missed Visit (Accounted for) | 0 | 0.0 | 0 | 0.0 | 2 | 0.7 | 0 | 0.0 | 0 | 0.0 | 4 | 1.4 | 12 | 4.1 | | Excluded from Efficacy Analysis | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | | % Accountability | | 100.0% | | 100.0% | | 99.3% | | 99.3% | | 99.3% | | 98.0% | | 95.2% | # b. Stability of Outcome Refractive stability was evaluated in the eyes that completed one or more pairs of successive postoperative visits. The mean changes (paired differences) in MRSE (± Standard Deviation (S.D). and 95% confidence interval (C.I.)) between pairs of successive refractions for eyes with all consecutive visits from Month 1 through Month 9 are reported in Tables 5 and 6, respectively, for eyes treated for spherical hyperopia and for those treated for hyperopic astigmatism. P970053/S009 SSED Page 13 of 36 20 {13} | TABLE 5 Refractive Stability for All Spherical Hyperopia Eyes that Underwent the 1 Week and 1, 3, 6, and 9 Month Visits | | | | | | | --- | --- | --- | --- | --- | --- | | | | WEEK 1 TO MONTH 1 | MONTH 1 TO MONTH 3 | MONTH 3 TO MONTH 6 | MONTH 6 TO MONTH 9 | | Change of MRSE ≤ 1D | n/N | 135/140 | 138/140 | 140/140 | 140/140 | | | (%) | (96.43%) | (98.57%) | (100.0%) | (100.0%) | | | (CI) | (93.4, 99.5) | (96.6, 100.0) | (97.4, 100.0) | (97.4, 100.0) | | Change of MRSE in diopters | Mean | 0.066 | 0.065 | 0.014 | 0.102 | | | Std | 0.49 | 0.37 | 0.28 | 0.32 | | | (CI) | (-0.05, 0.18) | (-0.04, 0.17) | (-0.07, 0.10) | (0.01, 0.20) | | Rate of Change (diopters/month) | | 0.066 | 0.033 | 0.005 | 0.034 | | TABLE 6 Refractive Stability for All Hyperopic Astigmatism Eyes that Underwent the 1 Week and 1, 3, 6, and 9 Month Visits | | | | | | | --- | --- | --- | --- | --- | --- | | | | WEEK 1 TO MONTH 1 | MONTH 1 TO MONTH 3 | MONTH 3 TO MONTH 6 | MONTH 6 TO MONTH 9 | | Change of MRSE ≤ 1D | n/N | 142/143 | 139/143 | 138/143 | 140/143 | | | (%) | (99.30%) | (97.20%) | (96.50%) | (97.90%) | | | (CI) | (97.9, 100.0) | (94.5, 99.9) | (93.5, 99.5) | (95.6, 100.0) | | Change of MRSE in diopters | Mean | 0.056 | 0.163 | 0.028 | 0.026 | | | Std | 0.32 | 0.40 | 0.43 | 0.39 | | | (CI) | (-0.04, 0.15) | (0.06, 0.27) | (-0.08, 0.14) | (-0.08, 0.13) | | Rate of Change | | 0.056 | 0.082 | 0.009 | 0.009 | Refractive stability was achieved at 6 months and confirmed at 9 months postoperatively for all the cohorts. The time point to refractive stability was 3 months for the spherical hyperopia eyes and 6 months for the hyperopic astigmatism eyes and the entire cohort of treated eyes. At the time point of refractive stability, the mean rate of change was 0.033 D/month for the spherical hyperopia cohort (at 3 months) and 0.009 D/month for the eyes treated for hyperopic astigmatism (at 6 months). # c. Effectiveness Outcomes The effectiveness analyses were based on 291 eyes that were available for analysis at 6 months postoperatively. A summary of key effectiveness variables is provided below in Table 7 for all eyes treated in the cohort. It is expected that at least 50% of the eyes will achieve a postoperative uncorrected visual acuity (UCVA) of 20/20 or better. The cohort of eyes in this study performed well in this P970053/S009 SSED Page 14 of 36 21 {14} category, with 59.8% (174/291) of all eyes treated having an UCVA of 20/20 or better at 6 months postoperatively, which is the time point of refractive stability. Results from the clinical study demonstrate that eyes treated for spherical hyperopia only and those treated for hyperopic astigmatism met or exceeded the target criteria established for the study. However, eyes treated for spherical hyperopia had a greater proportion that achieved 20/20 or better UCVA (69.4% for spherical cohort, 50.3% for astigmatic cohort), with the proportion achieving 20/40 or better UCVA being the same in both groups (98.6% for spherical and astigmatic cohorts). Similarly, eyes treated for spherical hyperopia had a greater proportion that were within ±0.5 D of attempted MRSE (77.1% for spherical cohort, 60.5% for astigmatic cohort) with the proportion within ±1.0 D of attempted MRSE being similar for both groups (95.1% for spherical cohort, 91.8% for astigmatic cohort). | TABLE 7 Key Effectiveness Outcomes for All Eyes Treated | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | EFFICACY VARIABLES | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | MRSE ± 0.50 D | n/N | 227/293 | 227/291 | 210/291 | 200/291 | 197/287 | 176/279 | | | (%) | (77.47%) | (78.01%) | (72.16%) | (68.73%) | (68.64%) | (63.08%) | | | (CI) | (72.6, 82.4) | (73.2, 82.9) | (66.9, 77.4) | (63.3, 74.2) | (63.2, 74.1) | (57.3, 68.9) | | MRSE ± 1.00 D | n/N | 281/293 | 278/291 | 272/291 | 272/291 | 268/287 | 252/279 | | | (%) | (95.90%) | (95.53%) | (93.47%) | (93.47%) | (93.38%) | (90.32%) | | | (CI) | (93.6, 98.2) | (93.1, 98.0) | (90.6, 96.4) | (90.6, 96.4) | (90.4, 96.3) | (86.8, 93.9) | | MRSE ± 2.00 D | n/N | 292/293 | 289/291 | 290/291 | 290/291 | 286/287 | 279/279 | | | (%) | (99.66%) | (99.31%) | (99.66%) | (99.66%) | (99.65%) | (100.0%) | | | (CI) | (99.0, 100.3) | (98.3, 100.3) | (99.0, 100.3) | (99.0, 100.3) | (99.0, 100.3) | (100.0, 100.0) | | UCVA 20/20 or better | n/N | 154/293 | 174/291 | 163/291 | 174/291 | 174/287 | 170/279 | | | (%) | (52.56%) | (59.79%) | (56.01%) | (59.79%) | (60.63%) | (60.93%) | | | (CI) | (46.7, 58.4) | (54.0, 65.5) | (50.2, 61.8) | (54.0, 65.5) | (54.9, 66.4) | (55.1, 66.8) | | UCVA 20/40 or better | n/N | 283/293 | 287/291 | 286/291 | 287/291 | 284/287 | 277/279 | | | (%) | (96.59%) | (98.63%) | (98.28%) | (98.63%) | (98.95%) | (99.28%) | | | (CI) | (94.5, 98.7) | (97.3, 100.0) | (96.8, 99.8) | (97.3, 100.0) | (97.8, 100.2) | (98.3, 100.3) | Efficacy outcomes for the eyes that are within the approved range (≤ +5.00 D sphere, ≤ +2.00 D cylinder, with ≤ +5.00 D MRSE) are summarized in Table 8 below. As would be expected at 6 months, the approved range cohort shows superior efficacy outcomes, with 72.0% of the eyes achieving a MRSE within ±0.50 D of the attempted parameters compared to 68.7% of the entire cohort. P970053/S009 SSED Page 15 of 36 22 {15} Similarly, 62.7% of the eyes in the approved range cohort had an UCVA of 20/20 or better at 6 months compared to 59.8% of the entire cohort. | TABLE 8 Key Effectiveness Outcomes Eyes Within the Approved Range | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | EFFICACY VARIABLES | | | | | | | | | MRSE ± 0.50 D | n/N | 212/270 | 214/268 | 198/268 | 193/268 | 189/265 | 166/256 | | | (%) | (78.52%) | (79.85%) | (73.88%) | (72.01%) | (71.32%) | (64.84%) | | MRSE ± 1.00 D | n/N | 259/270 | 259/268 | 254/268 | 254/268 | 250/265 | 234/256 | | | (%) | (95.93%) | (96.64%) | (94.78%) | (94.78%) | (94.34%) | (91.41%) | | MRSE ± 2.00 D | n/N | 269/270 | 266/268 | 267/268 | 267/268 | 264/265 | 256/256 | | | (%) | (99.63%) | (99.25%) | (99.63%) | (99.63%) | (99.62%) | (100.0%) | | UCVA 20/20 or better | n/N | 149/270 | 169/268 | 156/268 | 168/268 | 167/265 | 166/256 | | | (%) | (55.19%) | (63.06%) | (58.21%) | (62.69%) | (63.02%) | (64.84%) | | UCVA 20/40 or better | n/N | 262/270 | 266/268 | 264/268 | 266/268 | 262/265 | 254/256 | | | (%) | (97.04%) | (99.25%) | (98.51%) | (99.25%) | (98.87%) | (99.22%) | Summaries of key effectiveness parameters at Month 6 are stratified below by preoperative manifest refraction spherical equivalent (MRSE), preoperative manifest sphere, and preoperative manifest cylinder in Tables 9, 10, and 11, respectively. P970053/S009 SSED Page 16 of 36 23 {16} | TABLE 9 Key Effectiveness Outcomes at Month 6 Stratified by Baseline MRSE | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | MRSE (Diopters) | | 0.00 TO 1.00D | 1.01 TO 2.00D | 2.01 TO 3.00D | 3.01 TO 4.00D | 4.01 TO 5.00D | >5.00D | CUM TOTAL | | EFFICACY VARIABLES | | | | | | | | | | MRSE ± 0.50 D | n/N | 5/10 | 72/97 | 70/93 | 42/58 | 9/19 | 2/14 | 200/291 | | | (%) | (50.00%) | (74.23%) | (75.27%) | (72.41%) | (47.37%) | (14.29%) | (68.73%) | | MRSE ± 1.00 D | n/N | 10/10 | 96/97 | 86/93 | 54/58 | 16/19 | 10/14 | 272/291 | | | (%) | (100.0%) | (98.97%) | (92.47%) | (93.10%) | (84.21%) | (71.43%) | (93.47%) | | MRSE ± 2.00 D | n/N | 10/10 | 97/97 | 93/93 | 57/58 | 19/19 | 14/14 | 290/291 | | | (%) | (100.0%) | (100.0%) | (100.0%) | (98.28%) | (100.0%) | (100.0%) | (99.66%) | | UCVA 20/20 or better | n/N | 4/10 | 67/97 | 64/93 | 28/58 | 7/19 | 4/14 | 174/291 | | | (%) | (40.00%) | (69.07%) | (68.82%) | (48.28%) | (36.84%) | (28.57%) | (59.79%) | | UCVA 20/40 or better | n/N | 10/10 | 97/97 | 91/93 | 57/58 | 19/19 | 13/14 | 287/291 | | | (%) | (100.0%) | (100.0%) | (97.85%) | (98.28%) | (100.0%) | (92.86%) | (98.63%) | | TABLE 10 Key Effectiveness Outcomes at Month 6 Stratified by Baseline Sphere | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | 0.00 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 | | EFFICACY VARIABLES | | | | | | | | | | MRSE ± 0.50 D | n/N | 13/23 | 77/103 | 66/87 | 35/52 | 8/18 | 1/8 | 200/291 | | | (%) | (56.52%) | (74.76%) | (75.86%) | (67.31%) | (44.44%) | (12.50%) | (68.73%) | | MRSE ± 1.00 D | n/N | 23/23 | 101/103 | 79/87 | 48/52 | 15/18 | 6/8 | 272/291 | | | (%) | (100.0%) | (98.06%) | (90.80%) | (92.31%) | (83.33%) | (75.00%) | (93.47%) | | MRSE ± 2.00 D | n/N | 23/23 | 103/103 | 87/87 | 51/52 | 18/18 | 8/8 | 290/291 | | | (%) | (100.0%) | (100.0%) | (100.0%) | (98.08%) | (100.0%) | (100.0%) | (99.66%) | | UCVA 20/20 or better | n/N | 12/23 | 70/103 | 59/87 | 23/52 | 10/18 | 0/8 | 174/291 | | | (%) | (52.17%) | (67.96%) | (67.82%) | (44.23%) | (55.56%) | (0.00%) | (59.79%) | | UCVA 20/40 or better | n/N | 22/23 | 103/103 | 86/87 | 51/52 | 18/18 | 7/8 | 287/291 | | | (%) | (95.65%) | (100.0%) | (98.85%) | (98.08%) | (100.0%) | (87.50%) | (98.63%) | P970053/S009 SSED Page 17 of 36 24 {17} | TABLE 11 Key Effectiveness Outcomes at Month 6 Stratified by Baseline Cylinder | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | | | 0.00 TO 0.49D | 0.50 TO 1.00D | 1.01 TO 2.00D | 2.01 TO 3.00D | CUM TOTAL | | EFFICACY VARIABLES | | | | | | | | MRSE ± 0.50 D | n/N | 111/144 | 65/ 99 | 20/ 38 | 4/ 10 | 200/291 | | | (%) | (77.08%) | (65.66%) | (52.63%) | (40.00%) | (68.73%) | | MRSE ± 1.00 D | n/N | 137/144 | 92/ 99 | 36/ 38 | 7/ 10 | 272/291 | | | (%) | (95.14%) | (92.93%) | (94.74%) | (70.00%) | (93.47%) | | MRSE ± 2.00 D | n/N | 143/144 | 99/ 99 | 38/ 38 | 10/ 10 | 290/291 | | | (%) | (99.31%) | (100.0%) | (100.0%) | (100.0%) | (99.66%) | | UCVA 20/20 or better | n/N | 100/144 | 54/ 99 | 19/ 38 | 1/ 10 | 174/291 | | | (%) | (69.44%) | (54.55%) | (50.00%) | (10.00%) | (59.79%) | | UCVA 20/40 or better | n/N | 142/144 | 98/ 99 | 38/ 38 | 9/ 10 | 287/291 | | | (%) | (98.61%) | (98.99%) | (100.0%) | (90.00%) | (98.63%) | Eyes treated for spherical hyperopia or hyperopic astigmatism that have a baseline spherical component of manifest refraction of +5.00 D or less, a baseline spherical component of manifest refraction of +2.00 D or less, with an MRSE of +5.00 D or less show good efficacy and support the indicated range of approval. Eyes treated in the study also showed good improvement in functional vision. As shown in Table 12 below, 76% of the eyes achieved an uncorrected visual acuity (UCVA) postoperatively that was no worse than 1 line (5 letters) below the baseline best spectacle-corrected visual acuity (BSCVA) at Month 6. | TABLE 12 UCVA compared to Baseline BSCVA | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | UCVA ≥ 2 lines (≥10 letters) better than Baseline BSCVA | n/N | 5/293 | 9/291 | 3/291 | 3/291 | 4/287 | 3/279 | | | (%) | (1.71%) | (3.09%) | (1.03%) | (1.03%) | (1.39%) | (1.08%) | | | (CI) | (0.2, 3.2) | (1.1, 5.1) | (-0.2, 2.2) | (-0.2, 2.2) | (0.0, 2.8) | (-0.2, 2.3) | | UCVA within 1 line (5 letters) of Baseline BSCVA | n/N | 205/293 | 224/291 | 227/291 | 219/291 | 214/287 | 220/279 | | | (%) | (69.97%) | (76.98%) | (78.01%) | (75.26%) | (74.56%) | (78.85%) | | | (CI) | (64.6, 75.3) | (72.0, 81.9) | (73.2, 82.9) | (70.2, 80.3) | (69.4, 79.7) | (74.0, 83.7) | | UCVA ≥ 2 lines (≥10 letters) worse than Baseline BSCVA | n/N | 83/293 | 58/291 | 61/291 | 69/291 | 69/287 | 56/279 | | | (%) | (28.33%) | (19.93%) | (20.96%) | (23.71%) | (24.04%) | (20.07%) | | | (CI) | (23.1, 33.6) | (15.2, 24.6) | (16.2, 25.7) | (18.7, 28.7) | (19.0, 29.1) | (15.3, 24.9) | P970053/S009 SSED Page 18 of 36 25 {18} # d. Vector Analysis Vector analysis was performed on the cohort of eyes treated for hyperopic astigmatism. All vector analysis is based on the vector components vertex-corrected to the corneal plane. Cylinder stability calculated as the magnitude of cylinder vector differences is summarized in Table 13 below for each postoperative visit interval between Month 1 through Month 9. | TABLE 13 Magnitude of Cylinder Vector Differences | | | | | | | --- | --- | --- | --- | --- | --- | | | | MONTH 1 TO MONTH 3 | MONTH 3 TO MONTH 6 | MONTH 6 TO MONTH 9 | MONTH 9 TO MONTH 12 | | Magnitude of Cylinder Vector Difference ≤ 0.5 D | n/N | 102/147 | 95/147 | 109/144 | 111/141 | | | (%) | (69.39%) | (64.63%) | (75.69%) | (78.72%) | | | (CI) | (61.9, 76.8) | (56.9, 72.4) | (68.7, 82.7) | (72.0, 85.5) | | Magnitude of Cylinder Vector Difference ≤ 1D | n/N | 140/147 | 141/147 | 141/144 | 140/141 | | | (%) | (95.24%) | (95.92%) | (97.92%) | (99.29%) | | | (CI) | (91.8, 98.7) | (92.7, 99.1) | (95.6, 100.0) | (97.9, 100.0) | | Magnitude of Cylinder Vector Difference (diopters) | Mean | 0.343 | 0.361 | 0.273 | 0.244 | | | Std | 0.35 | 0.30 | 0.25 | 0.25 | | | (CI) | (0.25, 0.44) | (0.27, 0.45) | (0.19, 0.36) | (0.16, 0.33) | The magnitude of the cylinder vector difference plateaus and remains constant over time, with no more than a 0.088 D/month difference between intervals for any of the intervals after the 1 month postoperative visit. The stability of absolute (non-vector) cylinder is summarized in Table 14 below. The magnitude of the absolute vector difference was no more than 0.5 D for over 92% of subjects at all time intervals. Similarly, the absolute cylinder also remains constant over time, with no more than a 0.02D difference occurring between any of the intervals evaluated. P970053/S009 SSED Page 19 of 36 26 {19} | TABLE 14 Stability of Absolute (Non-Vector) Cylinder | | | | | | | --- | --- | --- | --- | --- | --- | | | | MONTH 1 TO MONTH 3 | MONTH 3 TO MONTH 6 | MONTH 6 TO MONTH 9 | MONTH 9 TO MONTH 12 | | Cylinder Magnitude Difference ≤ 0.5 D | n/N | 136/147 | 136/147 | 138/144 | 136/141 | | | (%) | (92.52%) | (92.52%) | (95.83%) | (96.45%) | | | (CI) | (88.3, 96.8) | (88.3, 96.8) | (92.6, 99.1) | (93.4, 99.5) | | Cylinder Magnitude Difference ≤ 1D | n/N | 145/147 | 146/147 | 144/144 | 141/141 | | | (%) | (98.64%) | (99.32%) | (100.0%) | (100.0%) | | | (CI) | (96.8, 100.0) | (98.0, 100.0) | (97.4, 100.0) | (97.4, 100.0) | | Cylinder Magnitude Difference (diopters) | Mean | 0.024 | 0.002 | 0.012 | 0.032 | | | Std | 0.37 | 0.37 | 0.29 | 0.27 | | | (CI) | (-0.07, 0.12) | (-0.10, 0.10) | (-0.08, 0.10) | (-0.05, 0.12) | The descriptive statistics for the predictability (accuracy) of the attempted versus achieved manifest sphere and magnitude of vector cylinder are summarized in Table 15 below for the entire cohort and in Table 16 for those eyes within the approved range (≤ +5.00 D sphere, ≤ +2.00 D cylinder, with ≤ +5.00 D MRSE). P970053/S009 SSED Page 20 of 36 27 {20} | TABLE 15 Treatment Accuracy for Sphere and Cylinder Magnitude | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | | BASELINE | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | SPHERE | N=293 | N=291 | N=291 | N=291 | N=287 | N=279 | | Mean (SD) | 2.48 (1.22) | -0.07 (0.58) | 0.05 (0.56) | 0.07 (0.56) | 0.12 (0.54) | 0.17 (0.56) | | Attempted (SD) | 2.48 (1.22) | 2.48 (1.23) | 2.47 (1.22) | 2.47 (1.22) | 2.47 (1.23) | 2.47 (1.23) | | Achieved (SD) | | 2.51 (1.46) | 2.39 (1.43) | 2.37 (1.43) | 2.29 (1.39) | 2.26 (1.43) | | % Achieved | | 97.64% | 91.75% | 91.05% | 88.56% | 85.73% | | ± 0.5D | | 68.73% | 64.60% | 61.17% | 62.28% | 60.57% | | ± 1.0D | | 93.13% | 92.10% | 93.13% | 91.70% | 88.89% | | CYLINDER | N=149 | N=149 | N=147 | N=147 | N=144 | N=142 | | Mean (SD) | 1.04 (0.60) | 0.38 (0.39) | 0.41 (0.44) | 0.42 (0.43) | 0.42 (0.49) | 0.45 (0.47) | | Attempted (SD) | 1.04 (0.60) | 1.04 (0.60) | 1.04 (0.60) | 1.04 (0.60) | 1.05 (0.60) | 1.04 (0.60) | | Achieved (SD) | | 0.65 (0.55) | 0.63 (0.60) | 0.62 (0.56) | 0.62 (0.62) | 0.59 (0.59) | | % Achieved | | 59.45% | 55.26% | 57.35% | 56.36% | 52.74% | | ± 0.5D | | 62.42% | 58.50% | 53.06% | 57.93% | 53.52% | | ± 1.0D | | 90.60% | 87.76% | 89.12% | 86.90% | 85.21% | Hyperopic astigmatic treatments performed with the EC-5000 excimer laser using the H70 treatment algorithm yielded excellent treatment results for vector cylinder. At the timepoint of refractive stability (6 months), the eyes in the entire hyperopic astigmatic cohort (see Table 15) achieved 92.4% of the attempted vector cylinder treatment and those that were in the approved range (see Table 16) achieved 93.6% of the attempted vector cylinder treatment. The results for the spherical component of the treatment were not as accurate, but were still good, with the entire cohort of hyperopic astigmatic eyes achieving 85.3% of the attempted spherical treatment and the eyes in the approved cohort achieving 83.3% of the attempted spherical treatment. The percentage of vector cylinder achieved remains constant after 3 months, as does the percentage of spherical treatment achieved. P970053/S009 SSED Page 21 of 36 28 {21} | TABLE 16 Treatment Accuracy for Sphere and Cylinder Magnitude For Eyes within the Approved Ranges | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | | BASELINE | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | SPHERE | N=270 | N=268 | N=268 | N=268 | N=265 | N=256 | | Mean (SD) | 2.31 (1.01) | -0.06 (0.56) | 0.05 (0.55) | 0.08 (0.54) | 0.12 (0.54) | 0.17 (0.56) | | Attempted (SD) | 2.31 (1.01) | 2.31 (1.01) | 2.31 (1.01) | 2.31 (1.01) | 2.30 (1.01) | 2.29 (1.01) | | Achieved (SD) | | 2.33 (1.27) | 2.22 (1.24) | 2.19 (1.24) | 2.14 (1.22) | 2.08 (1.23) | | % Achieved | | 97.41% | 91.73% | 90.27% | 88.66% | 85.53% | | ± 0.5D | | 71.27% | 66.42% | 63.81% | 64.29% | 61.72% | | ± 1.0D | | 94.03% | 92.91% | 93.66% | 92.11% | 89.06% | | CYLINDER | N=128 | N=128 | N=126 | N=126 | N=124 | N=121 | | Mean (SD) | 0.90 (0.40) | 0.32 (0.33) | 0.34 (0.35) | 0.34 (0.36) | 0.36 (0.43) | 0.37 (0.40) | | Attempted (SD) | 0.90 (0.40) | 0.90 (0.40) | 0.90 (0.40) | 0.90 (0.40) | 0.90 (0.40) | 0.90 (0.40) | | Achieved (SD) | | 0.57 (0.45) | 0.56 (0.53) | 0.55 (0.49) | 0.54 (0.53) | 0.52 (0.52) | | % Achieved | | 60.02% | 55.69% | 58.34% | 56.88% | 53.38% | | ± 0.5D | | 67.19% | 63.49% | 59.52% | 62.90% | 58.68% | | ± 1.0D | | 94.53% | 92.06% | 92.86% | 89.52% | 91.74% | A summary of the intended refractive correction (IRC), surgically induced refractive correction (SIRC), correction ratio (CR), and error ratio (ER) at 6 months postoperatively (timepoint of stability) is provided in Table 17 below. | TABLE 17 Refractive Correction Parameters Stratified by Preoperative Cylinder | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | VISIT | CYLINDER GROUP* | N | IRC MEAN(SD) | SIRC MEAN(SD) | CR MEAN(SD) | ER MEAN(SD) | | POSTOP MONTH 6 | ALL | 147 | 1.04 (0.60) | 0.92 (0.54) | 0.92 (0.30) | 0.42 (0.43) | | | 0.5D-1.0D | 87 | 0.66 (0.14) | 0.64 (0.25) | 0.97 (0.31) | 0.47 (0.50) | | | >1.0D-2.0D | 50 | 1.37 (0.27) | 1.18 (0.40) | 0.86 (0.28) | 0.36 (0.32) | | | >2.0D-3.0D | 8 | 2.56 (0.19) | 1.92 (0.73) | 0.76 (0.30) | 0.39 (0.25) | | | >3.0D-4.0D | 2 | 3.27 (0.14) | 2.60 (1.15) | 0.80 (0.39) | 0.42 (0.15) | (*Cylinder group based on cylinder correction at the corneal plane) P970053/S009 SSED Page 22 of 36 29 {22} At 6 months postoperatively, the SIRC of 0.92 for the hyperopic astigmatism cohort closely approximates the intended refractive correction for all eyes treated. This is confirmed by the correction ratio (CR) of 0.92 for all treated eyes in the cohort. Outcomes in higher cylindrical ranges are consistent with those observed in other contemporary LASIK clinical trials. The number of eyes that are within ±0.5 D, ±1.0 D, and ±2.0 D of attempted versus achieved manifest refraction spherical equivalent (MRSE) and the proportion of eyes that were overcorrected or undercorrected at each of the postoperative examinations are summarized in Table 18 below for eyes treated for hyperopic astigmatism and in Table 19 for eyes treated for spherical hyperopia. | TABLE 18 Accuracy of Attempted vs. Achieved MRSE Refractive Correction Eyes Treated for Hyperopic Astigmatism | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | Achieved MRSE | | PREOP | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | ± 0.5 D | n/N | 0/149 | 111/149 | 95/147 | 89/147 | 89/144 | 82/142 | | | (%) | (0.00%) | (74.50%) | (64.63%) | (60.54%) | (61.81%) | (57.75%) | | ± 1.0 D | n/N | 6/149 | 141/149 | 134/147 | 135/147 | 129/144 | 122/142 | | | (%) | (4.03%) | (94.63%) | (91.16%) | (91.84%) | (89.58%) | (85.92%) | | ± 2.0 D | n/N | 49/149 | 149/149 | 147/147 | 147/147 | 144/144 | 142/142 | | | (%) | (32.89%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | (100.0%) | | Undercorrected > +1.0 D | n/N | 143/149 | 8/149 | 13/147 | 12/147 | 15/144 | 20/142 | | | (%) | (95.97%) | (5.37%) | (8.84%) | (8.16%) | (10.42%) | (14.08%) | | Undercorrected > +2.0 D | n/N | 100/149 | 0/149 | 0/147 | 0/147 | 0/144 | 0/142 | | | (%) | (67.11%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | Overcorrected < -1.0 D | n/N | 0/149 | 0/149 | 0/147 | 0/147 | 0/144 | 0/142 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | Overcorrected < -2.0 D | n/N | 0/149 | 0/149 | 0/147 | 0/147 | 0/144 | 0/142 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | Overall at 6 months postoperatively, 68.7% (200/291) of all the eyes treated were within ± 0.5 D of the attempted refraction and 93.5% (272/291) of the eyes were within ± 1.0 D of the attempted refraction. Similar results were observed in the individual cohorts, with 95.1% (135/144) of the eyes treated for spherical hyperopia (Table 19) and 91.8% (135/147) of the hyperopic astigmatic eyes (Table 18) within ±1.0 D of attempted MRSE. None of the eyes (0/291; 0.0%) in the study was undercorrected by more than 2.0 D MRSE and only one eye (1/291; 0.3%) was overcorrected by more than 2.0 D MRSE at 6 months postoperatively. The subject with the overcorrected spherical hyperopia eye developed bilateral posterior subcapsular cataracts, which became evident on the slit lamp examination at the 6 month examination. Obtaining a reliable and accurate manifest refraction was difficult in this subject because of the cataracts. P970053/S009 SSED Page 23 of 36 30 {23} | TABLE 19 Accuracy of Attempted vs. Achieved MRSE Refractive Correction Eyes Treated for Spherical Hyperopia | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | Achieved MRSE | | PREOP | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | ± 0.5 D | n/N | 1/144 | 116/142 | 115/144 | 111/144 | 108/143 | 94/137 | | | (%) | (0.69%) | (81.69%) | (79.86%) | (77.08%) | (75.52%) | (68.61%) | | ± 1.0 D | n/N | 8/144 | 137/142 | 138/144 | 137/144 | 139/143 | 130/137 | | | (%) | (5.56%) | (96.48%) | (95.83%) | (95.14%) | (97.20%) | (94.89%) | | ±2.0 D | n/N | 63/144 | 140/142 | 143/144 | 143/144 | 142/143 | 137/137 | | | (%) | (43.75%) | (98.59%) | (99.31%) | (99.31%) | (99.30%) | (100.0%) | | Uncorrected > +1.0 D | n/N | 136/144 | 1/142 | 1/144 | 2/144 | 2/143 | 4/137 | | | (%) | (94.44%) | (0.70%) | (0.69%) | (1.39%) | (1.40%) | (2.92%) | | Undercorrected > +2.0 D | n/N | 81/144 | 0/142 | 0/144 | 0/144 | 0/143 | 0/137 | | | (%) | (56.25%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | Overcorrected < -1.0 D | n/N | 0/144 | 4/142 | 5/144 | 5/144 | 2/143 | 3/137 | | | (%) | (0.00%) | (2.82%) | (3.47%) | (3.47%) | (1.40%) | (2.19%) | | Overcorrected < -2.0 D | n/N | 0/144 | 2/142 | 1/144 | 1/144 | 1/143 | 0/137 | | | (%) | (0.00%) | (1.41%) | (0.69%) | (0.69%) | (0.70%) | (0.00%) | The mean percent reduction in absolute (non-vector) cylinder is shown in Table 20 below. | TABLE 20 Percent Reduction in Absolute (Non-Vector) Cylinder | | | | --- | --- | --- | | Cylinder Group* | n | Mean (range) Percent Reduction | | All hyperopic astigmatism eyes | 145 | 57.6% (15.0% - 100.0%) | | ≥ 0.5 D to ≤ 1.0 D | 87 | 53.2% (-134.5% to - 100.0%) | | > 1.0 D to ≤ 2.0 D | 50 | 64.7% (-21.2% to - 100.0%) | | > 2.0 D to ≤ 3.0 D | 8 | 60.5% (15.0% to - 100.0%) | (*Cylinder group based on cylinder correction at the corneal plane) P970053/S009 SSED Page 24 of 36 31 {24} # c. Safety Outcomes The safety analyses were based on 291 eyes that were available for analysis at 6 months postoperatively. A summary of key safety variables is provided below in Tables 21, 22, and 23 for all eyes treated in the cohort and the individual cohorts and are stratified by baseline manifest refraction spherical equivalent in Table 24. | TABLE 21 Summary of Key Safety Variables for All Eyes Treated | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | SAFETY VARIABLES | | | | | | | | | Loss of 2 or more lines (≥10 letters) BSCVA | n/N | 12/293 | 2/291 | 4/290 | 10/291 | 11/287 | 4/279 | | | (%) | (4.10%) | (0.69%) | (1.38%) | (3.44%) | (3.83%) | (1.43%) | | BSCVA worse than 20/40 | n/N | 0/293 | 0/291 | 0/290 | 0/291 | 0/287 | 0/279 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | Increase > 2D cylinder | n/N | 0/293 | 1/291 | 1/291 | 1/291 | 2/287 | 1/279 | | | (%) | (0.00%) | (0.34%) | (0.34%) | (0.34%) | (0.70%) | (0.36%) | | BSCVA worse than 20/25 if 20/20 or better preop | n/N | 3/270 | 0/268 | 1/267 | 1/268 | 3/265 | 3/257 | | | (%) | (1.11%) | (0.00%) | (0.37%) | (0.37%) | (1.13%) | (1.17%) | | TABLE 22 Summary of Key Safety Variables for Eyes Treated for Spherical Hyperopia | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | SAFETY VARIABLES | | | | | | | | | Loss of 2 or more lines (≥10 letters) BSCVA | n/N | 5/144 | 1/142 | 2/143 | 6/144 | 6/143 | 3/137 | | | (%) | (3.47%) | (0.70%) | (1.40%) | (4.17%) | (4.20%) | (2.19%) | | BSCVA worse than 20/40 | n/N | 0/144 | 0/142 | 0/143 | 0/144 | 0/143 | 0/137 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | Increase > 2D cylinder | n/N | 0/144 | 1/142 | 1/144 | 1/144 | 2/143 | 1/137 | | | (%) | (0.00%) | (0.70%) | (0.69%) | (0.69%) | (1.40%) | (0.73%) | | BSCVA worse than 20/25 if 20/20 or better preop | n/N | 1/141 | 0/139 | 1/140 | 1/141 | 2/140 | 2/134 | | | (%) | (0.71%) | (0.00%) | (0.71%) | (0.71%) | (1.43%) | (1.49%) | P970053/S009 SSED Page 25 of 36 32 {25} | TABLE 23 Summary of Key Safety Variables for Eyes Treated for Hyperopic Astigmatism | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | SAFETY VARIABLES | | | | | | | | | Loss of 2 or more lines (≥10 letters) BSCVA | n/N | 7/149 | 1/149 | 2/147 | 4/147 | 5/144 | 1/142 | | | (%) | (4.70%) | (0.67%) | (1.36%) | (2.72%) | (3.47%) | (0.70%) | | BSCVA worse than 20/40 | n/N | 0/149 | 0/149 | 0/147 | 0/147 | 0/144 | 0/142 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | Increase > 2D cylinder | n/N | 0/149 | 0/149 | 0/147 | 0/147 | 0/144 | 0/142 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | BSCVA worse than 20/25 if 20/20 or better preop | n/N | 2/129 | 0/129 | 0/127 | 0/127 | 1/125 | 1/123 | | | (%) | (1.55%) | (0.00%) | (0.00%) | (0.00%) | (0.80%) | (0.81%) | | TABLE 24 Key Safety Outcomes at Month 6 Stratified by Baseline MRSE | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | MRSE (Diopters) | | 0.00 TO 1.00D | 1.01 TO 2.00D | 2.01 TO 3.00D | 3.01 TO 4.00D | 4.01 TO 5.00D | >5.00D | CUM TOTAL | | EFFICACY VARIABLES | | | | | | | | | | Loss of 2 or more lines (≥10 letters) BSCVA | n/N | 0/3 | 1/57 | 1/46 | 4/28 | 0/8 | 0/2 | 6/144 | | | (%) | (0.00%) | (1.75%) | (2.17%) | (14.29%) | (0.00%) | (0.00%) | (4.17%) | | BSCVA worse than 20/40 | n/N | 0/3 | 0/57 | 0/46 | 0/28 | 0/8 | 0/2 | 0/144 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | Increase > 2D cylinder | n/N | 0/3 | 0/57 | 0/46 | 1/28 | 0/8 | 0/2 | 1/144 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (3.57%) | (0.00%) | (0.00%) | (0.69%) | | BSCVA worse than 20/25 if 20/20 or better preop | n/N | 0/3 | 0/56 | 0/44 | 1/28 | 0/8 | 0/2 | 1/141 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (3.57%) | (0.00%) | (0.00%) | (0.71%) | Very little loss of BSCVA occurred in the majority of eyes treated in the study, with 1% or less of the eyes at any postoperative exam reporting a BSCVA worse than 20/25 if the preoperative BSCVA was 20/20 or better. The incidence of new reports of loss of 2 or more lines (≥10 letters) of BSCVA was 1.4% at Month 3, 2.4% at Month 6, 2.1% at Month 9, and 0.7% at Month 12. The overall cumulative rate was 6.5% (19/293 eyes) for the cohort, of which 1.4% (4/293 eyes) had a persistent loss of at least 2 lines (10 letters) of BSCVA; last visit BSCVA was 20/20 for 1 eye, 20/32 for 2 eyes, and 20/40 for 1 eye that had a concomitant posterior subcapsular cataract that diminished the BSCVA. Changes in BSCVA from baseline to each postoperative visit are summarized in Tables 25, 26, and 27 for all eyes treated and the individual cohorts. P970053/S009 SSED Page 26 of 36 33 {26} | TABLE 25 Changes in BSCVA from Preop to Postop for All Eyes Treated | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | Decrease > 2 Lines | n/N | 0/293 | 0/291 | 0/290 | 1/291 | 1/287 | 1/279 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.34%) | (0.35%) | (0.36%) | | | (CI) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (-0.3, 1.0) | (-0.3, 1.0) | (-0.4, 1.1) | | Decrease 2 Lines | n/N | 12/293 | 2/291 | 4/290 | 9/291 | 10/287 | 3/279 | | | (%) | (4.10%) | (0.69%) | (1.38%) | (3.09%) | (3.48%) | (1.08%) | | | (CI) | (1.8, 6.4) | (-0.3, 1.7) | (0.0, 2.7) | (1.1, 5.1) | (1.3, 5.6) | (-0.2, 2.3) | | Decrease 1 Line | n/N | 68/293 | 47/291 | 47/290 | 53/291 | 48/287 | 43/279 | | | (%) | (23.21%) | (16.15%) | (16.21%) | (18.21%) | (16.72%) | (15.41%) | | | (CI) | (18.3, 28.1) | (11.8, 20.5) | (11.9, 20.5) | (13.7, 22.7) | (12.3, 21.1) | (11.1, 19.7) | | No Change | n/N | 158/293 | 165/291 | 165/290 | 154/291 | 166/287 | 158/279 | | | (%) | (53.92%) | (56.70%) | (56.90%) | (52.92%) | (57.84%) | (56.63%) | | | (CI) | (48.1, 59.7) | (50.9, 62.5) | (51.1, 62.7) | (47.1, 58.8) | (52.0, 63.7) | (50.7, 62.6) | | Increase 1 Line | n/N | 48/293 | 64/291 | 60/290 | 67/291 | 55/287 | 71/279 | | | (%) | (16.38%) | (21.99%) | (20.69%) | (23.02%) | (19.16%) | (25.45%) | | | (CI) | (12.1, 20.7) | (17.1, 26.8) | (15.9, 25.4) | (18.1, 28.0) | (14.5, 23.8) | (20.2, 30.7) | | Increase 2 Lines | n/N | 3/293 | 9/291 | 12/290 | 7/291 | 7/287 | 3/279 | | | (%) | (1.02%) | (3.09%) | (4.14%) | (2.41%) | (2.44%) | (1.08%) | | | (CI) | (-0.2, 2.2) | (1.1, 5.1) | (1.8, 6.5) | (0.6, 4.2) | (0.6, 4.3) | (-0.2, 2.3) | | Increase > 2 Lines | n/N | 4/293 | 4/291 | 2/290 | 0/291 | 0/287 | 0/279 | | | (%) | (1.37%) | (1.37%) | (0.69%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (0.0, 2.7) | (0.0, 2.7) | (-0.3, 1.7) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | P970053/S009 SSED Page 27 of 36 34 {27} | TABLE 26 Changes in BSCVA from Preop to Postop for Spherical Hyperopia Eyes | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | Decrease > 2 Lines | n/N | 0/144 | 0/142 | 0/143 | 1/144 | 1/143 | 1/137 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.69%) | (0.70%) | (0.73%) | | | (CI) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (-0.7, 2.1) | (-0.7, 2.1) | (-0.7, 2.2) | | Decrease 2 Lines | n/N | 5/144 | 1/142 | 2/143 | 5/144 | 5/143 | 2/137 | | | (%) | (3.47%) | (0.70%) | (1.40%) | (3.47%) | (3.50%) | (1.46%) | | | (CI) | (0.4, 6.5) | (-0.7, 2.1) | (-0.6, 3.4) | (0.4, 6.5) | (0.4, 6.6) | (-0.6, 3.5) | | Decrease 1 Line | n/N | 32/144 | 22/142 | 18/143 | 23/144 | 18/143 | 15/137 | | | (%) | (22.22%) | (15.49%) | (12.59%) | (15.97%) | (12.59%) | (10.95%) | | | (CI) | (15.3, 29.2) | (9.4, 21.6) | (7.0, 18.1) | (9.9, 22.1) | (7.0, 18.1) | (5.6, 16.3) | | No Change | n/N | 83/144 | 83/142 | 83/143 | 81/144 | 90/143 | 86/137 | | | (%) | (57.64%) | (58.45%) | (58.04%) | (56.25%) | (62.94%) | (62.77%) | | | (CI) | (49.4, 65.9) | (50.2, 66.7) | (49.8, 66.3) | (48.0, 64.5) | (54.9, 71.0) | (54.5, 71.0) | | Increase 1 Line | n/N | 20/144 | 27/142 | 32/143 | 28/144 | 26/143 | 31/137 | | | (%) | (13.89%) | (19.01%) | (22.38%) | (19.44%) | (18.18%) | (22.63%) | | | (CI) | (8.1, 19.7) | (12.4, 25.6) | (15.4, 29.3) | (12.8, 26.0) | (11.7, 24.6) | (15.5, 29.8) | | Increase 2 Lines | n/N | 1/144 | 7/142 | 7/143 | 6/144 | 3/143 | 2/137 | | | (%) | (0.69%) | (4.93%) | (4.90%) | (4.17%) | (2.10%) | (1.46%) | | | (CI) | (-0.7, 2.1) | (1.3, 8.6) | (1.3, 8.5) | (0.8, 7.5) | (-0.3, 4.5) | (-0.6, 3.5) | | Increase > 2 Lines | n/N | 3/144 | 2/142 | 1/143 | 0/144 | 0/143 | 0/137 | | | (%) | (2.08%) | (1.41%) | (0.70%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (-0.3, 4.5) | (-0.6, 3.4) | (-0.7, 2.1) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | P970053/S009 SSED Page 28 of 36 35 {28} | TABLE 27 Changes in BSCVA from Preop to Postop for Hyperopic Astigmatism Eyes | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | WEEK 1 | MONTH 1 | MONTH 3 | MONTH 6 | MONTH 9 | MONTH 12 | | Decrease > 2 Lines | n/N | 0/149 | 0/149 | 0/147 | 0/147 | 0/144 | 0/142 | | | (%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | | Decrease 2 Lines | n/N | 7/149 | 1/149 | 2/147 | 4/147 | 5/144 | 1/142 | | | (%) | (4.70%) | (0.67%) | (1.36%) | (2.72%) | (3.47%) | (0.70%) | | | (CI) | (1.2, 8.2) | (-0.7, 2.0) | (-0.6, 3.3) | (0.0, 5.4) | (0.4, 6.5) | (-0.7, 2.1) | | Decrease 1 Line | n/N | 36/149 | 25/149 | 29/147 | 30/147 | 30/144 | 26/142 | | | (%) | (24.16%) | (16.78%) | (19.73%) | (20.41%) | (20.83%) | (19.72%) | | | (CI) | (17.1, 31.2) | (10.7, 22.9) | (13.2, 26.3) | (13.8, 27.1) | (14.1, 27.6) | (13.0, 26.4) | | No Change | n/N | 75/149 | 82/149 | 82/147 | 73/147 | 76/144 | 72/142 | | | (%) | (50.34%) | (55.03%) | (55.78%) | (49.66%) | (52.78%) | (50.70%) | | | (CI) | (42.1, 58.5) | (46.9, 63.2) | (47.6, 64.0) | (41.4, 57.9) | (44.5, 61.1) | (42.3, 59.1) | | Increase 1 Line | n/N | 28/149 | 37/149 | 28/147 | 39/147 | 29/144 | 40/142 | | | (%) | (18.79%) | (24.83%) | (19.05%) | (26.53%) | (20.14%) | (28.17%) | | | (CI) | (12.4, 25.2) | (17.8, 31.9) | (12.6, 25.5) | (19.2, 33.8) | (13.5, 26.8) | (20.6, 35.7) | | Increase 2 Lines | n/N | 2/149 | 2/149 | 5/147 | 1/147 | 4/144 | 1/142 | | | (%) | (1.34%) | (1.34%) | (3.40%) | (0.68%) | (2.78%) | (0.70%) | | | (CI) | (-0.5, 3.2) | (-0.5, 3.2) | (0.4, 6.4) | (-0.7, 2.0) | (0.0, 5.5) | (-0.7, 2.1) | | Increase > 2 Lines | n/N | 1/149 | 2/149 | 1/147 | 0/147 | 0/144 | 0/142 | | | (%) | (0.67%) | (1.34%) | (0.68%) | (0.00%) | (0.00%) | (0.00%) | | | (CI) | (-0.7, 2.0) | (-0.5, 3.2) | (-0.7, 2.0) | (0.0, 0.0) | (0.0, 0.0) | (0.0, 0.0) | The adverse events and complications that occurred during the clinical study are summarized in Tables 28 and 29, respectively, below. P970053/S009 SSED Page 29 of 36 36 {29} | TABLE 28 Adverse Events | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Intraop | 1 Day | 1 Wk | 1 Mo | 3 Mo | 6 Mo | 9 Mo | 12 Mo | | ADVERSE EVENTS | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | | Diffuse lamellar keratitis with progressive melt | | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Corneal infiltrate or ulcer | | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Any corneal epithelial defect involving keratectomy site at 1 month or later | | | | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Corneal edema at 1 month or later | | | | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Epithelium in interface with loss of 2 or more lines (≥10 letters) of BSCVA | | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Miscreated flap (lost, incomplete, too thin) | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Melting of the flap | | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | IOP on 2 consecutive exams that is increase of > 10 mm Hg above baseline or > 30 mm Hg | | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Haze beyond 6 mos. with loss of ≥2 lines (≥10 letters) BSCVA | | | | | | | 0.0% (0/285) | 0.0% (0/232) | | Decrease of BSCVA of 2 or more lines (≥ 10 letters) not due to irregular astigmatism as shown by hard contact lens refraction at 3 months or later^{1} | | | | | 1.4% (4/291) | 2.4% (7/291) | 2.1% (6/285) | 0.4% (1/232) | | Retinal detachment | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Retinal vascular accidents | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Any other vision threatening event | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Ocular penetration | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | No adverse events occurred in the study except loss of 2 or more lines (≥10 letters) of BSCVA. Of the eyes that lost BSCVA at 6 months or later, all but 2 eyes had a preoperative BSCVA of 20/16 or better and these eyes did not have the ability to gain lines of BSCVA. The incidence of postoperative complications is summarized in Table 29 below. $^{1}$ The incidence of new reports of loss of 2 or more lines (≥10 letters) of BSCVA was 1.4% at Month 3, 2.4% at Month 6, 2.1% at Month 9, and 0.7% at Month 12. The overall cumulative rate was 6.5% (19/293 eyes) for the cohort, of which 1.4% (4/293 eyes) had a persistent loss of at least 2 lines (10 letters) of BSCVA. last visit BSCVA was 20/20 for 1 eye, 20/32 for 2 eyes, and 20/40 for 1 eye that had a concomitant posterior subcapsular cataract that diminished the BSCVA. P970053/S009 SSED Page 30 of 36 37 {30} | TABLE 29 Complications | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Intraop | 1 Day | 1 Wk | 1 Mo | 3 Mo | 6 Mo | 9 Mo | 12 Mo | | COMPLICATIONS | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | | Corneal edema between 1 week and 1 month after procedure | | | 0.7% (2/293) | 0.0% (0/291) | | | | | | Peripheral corneal epithelial defect at 1 month or later | | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.3% (1/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Epithelium in interface | | 0.7% (2/293) | 0.0% (0/293) | 0.0% (0/291) | 0.3% (1/291) | 0.0% (0/291) | 0.0% (0/285) | 0.4% (1/232) | | Foreign body sensation at 1 month or later | | | | 1.0% (3/291) | 0.0% (0/291) | 0.0% (0/291) | 0.4% (1/285) | 0.0% (0/232) | | Pain at 1 month or later | | | | 1.4% (4/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Ghost/double images in the operative eye | | 0.0% (0/293) | 0.0% (0/293) | 0.7% (2/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Flap is not of the size and shape as initially intended or microkeratome stopped mid-cut | 0.3% (1/293) | 0.0% (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Diffuse lamellar keratitis | | 3.1% (9/293) | 0.7% (2/293) | 0.7% (2/291) | 0.3% (1/291) | 0.0% (0/291) | 0.0% (0/285) | 0.0% (0/232) | | Dry eyes requiring punctal plugs or prescribed use of ocular lubricants at 1 month or later | | | | 2.7% (8/291) | 0.3% (1/291) | 1.4% (4/291) | 0.0% (0/285) | 0.0% (0/232) | The complications with an incidence of >1% at any visit were DLK, pain, foreign body sensation (FBS), and dry eye requiring prescribed ocular lubricants (the most common complication; Month 1, 2.7%; and Month 6, 1.4%). Other postoperative observations that occurred during the study are summarized in Table 30 below. P970053/S009 SSED Page 31 of 36 38 {31} | Table 30 Postoperative Observations for All Eyes Treated | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Intraop | 1 Day | 1 Wk | 1 Mo | 3 Mo | 6 Mo | 9 Mo | 12 Mo | | Observations | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | % (n/N) | | Blepharitis | | 0.0 % (0/293) | 0.0% (0/293) | 0.7% (2/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Chalazion | | 0.0 % (0/293) | 0.0% (0/293) | 0.7% (2/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Conjunctivitis, allergic | | 0.0 % (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.7 (2/285) | 0.0 % (0/232) | | Discomfort | | 0.0 % (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.7% (2/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Epithelial abrasion | 0.3% (1/293) | 0.0 % (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Epithelial basement membrane degeneration | | 0.0 % (0/293) | 0.3% (1/293) | 0.3% (1/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Hordeolum | | 0.0 % (0/293) | 0.0% (0/293) | 0.3% (1/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Interface blood | | 0.3% (1/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Laceration, lid | 0.7% (2/293) | 0.0 % (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Lens opacity | | 0.0 % (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 1.0% (3/291) | 0.0 % (0/285) | 0.9% (2/232) | | Misaligned flap | | 0.3% (1/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | PEK 3+ | | 0.0 % (0/293) | 0.7% (2/293) | 0.0% (0/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Photophobia | | 0.0 % (0/293) | 0.0 % (0/293) | 0.7% (2/291) | 0.0% (0/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Sheen in interface | | 5.8% (17/293) | 3.4% (10/293) | 6.9% (20/291) | 4.5% (13/291) | 4.1% (12/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Striae | | 0.0 % (0/293) | 0.3% (1/293) | 0.7% (2/291) | 0.3% (1/291) | 0.0% (0/291) | 0.0 % (0/285) | 0.0 % (0/232) | | Tearing, excessive | | 0.0 % (0/293) | 0.0% (0/293) | 0.0% (0/291) | 0.0% (0/291) | 0.3% (1/291) | 0.4% (1/285) | 0.0 % (0/232) | The most commonly occurring postoperative observation was that of sheen in interface that developed transiently (1 Day, 5.8%; 1 Week, 3.4%; 1 Month, 6.9%; 3 Months, 4.5%; 6 Months, 4.1%; and, 0% thereafter). Lamellar sheen is not unique to this study, having been observed by international Nidek users. Lamellar sheen occurs after Nidek EC-5000 hyperopic LASIK in the lamellar bed and is randomly distributed in the central cornea. The sheen appears as a faint dusting in the interface that is spotty and grayish in color with feathered edges and an orange-peel texture. In some cases, reflective patches give the surface a slight shiny appearance, hence the term sheen. [NOTE: The lamellar sheen observed after hyperopic LASIK is different from subepithelial stromal haze that occurs after PRK (diffuse, gray, granular confluence) and is also different from DLK (diffuse lamellar keratitis with a granular 'Sands of Sahara' appearance, associated with ocular inflammation). P970053/S009 SSED Page 32 of 36 39 {32} All cases of lamellar sheen in the study were transient, beginning 1 day to 6 months after surgery, lasting 1 week to 6 months, and resolving without treatment. No cases were observed after the 6 month examination. Lamellar sheen did not affect visual acuity in most cases, although it likely contributed to a transient loss of 2 lines (10 letters) of BSCVA in 7 eyes in the study (each of which returned to within 1 line (5 letters) of baseline BSCVA and a final BSCVA of 20/20 or better upon resolution of the sheen). At the 6 month examination, there was no statistically significant difference in BSCVA between eyes with and without sheen. The results of the subjective questionnaire at baseline and at the 6- and 12-month examinations are summarized by symptom in Table 31 below. Subjective visual complaints were obtained from each subject using a 10-point questionnaire to record symptoms. Visual complaints were recorded for each eye, and severity was classified as being either: "none," "mild," "moderate," "marked," or "severe." "Postoperative spectacle/contact lens use" and "patient satisfaction with LASIK outcome" were not included as specific questions on the visual complaint questionnaire and, therefore, were not evaluated in the PMA clinical trial. Visual symptoms after hyperopic LASIK were generally mild in severity. The reduction in post-operative complaints of difficulty reading and the increase in complaints about eye dryness were both clinically significant, defined as a change of ±10% or more in the proportion of eyes reporting symptoms that were moderate to severe postoperatively compared to baseline. P970053/S009 SSED Page 33 of 36 40 {33} TABLE 31 SUBJECTIVE COMPLAINTS | QUESTION | VISIT | NONE | MILD | MODERATE | MARKED | SEVERE | | --- | --- | --- | --- | --- | --- | --- | | LIGHT SENSITIVITY | SCREENING | 207/293 (71%) | 59/293 (20%) | 17/293 (6%) | 6/293 (2%) | 4/293 (1%) | | | POSTOP MONTH 6 | 211/291 (73%) | 66/291 (23%) | 10/291 (3%) | 4/291 (1%) | 0/291 (0%) | | | POSTOP MONTH 12 | 218/276 (79%) | 40/276 (14%) | 14/276 (5%) | 2/276 (1%) | 2/276 (1%) | | DIFFICULTY NIGHT DRIVING | SCREENING | 199/293 (68%) | 57/293 (19%) | 27/293 (9%) | 7/293 (2%) | 3/293 (1%) | | | POSTOP MONTH 6 | 243/291 (84%) | 39/291 (13%) | 8/291 (3%) | 1/291 (0%) | 0/291 (0%) | | | POSTOP MONTH 12 | 221/276 (80%) | 40/276 (14%) | 13/276 (5%) | 2/276 (1%) | 0/276 (0%) | | DIFFICULTY READING^{2} | SCREENING | 146/293 (50%) | 54/293 (18%) | 61/293 (21%) | 22/293 (8%) | 10/293 (3%) | | | POSTOP MONTH 6 | 153/289 (53%) | 86/289 (30%) | 30/289 (10%) | 16/289 (6%) | 4/289 (1%) | | | POSTOP MONTH 12 | 131/276 (47%) | 88/276 (32%) | 39/276 (14%) | 16/276 (6%) | 2/276 (1%) | | DOUBLE VISION | SCREENING | 285/293 (97%) | 6/293 (2%) | 1/293 (0%) | 0/293 (0%) | 1/293 (0%) | | | POSTOP MONTH 6 | 278/291 (96%) | 7/291 (2%) | 6/291 (2%) | 0/291 (0%) | 0/291 (0%) | | | POSTOP MONTH 12 | 263/287 (92%) | 20/287 (7%) | 4/287 (1%) | 0/287 (0%) | 0/287 (0%) | | FLUCTUATION IN VISION | SCREENING | 254/293 (87%) | 32/293 (11%) | 7/293 (2%) | 0/293 (0%) | 0/293 (0%) | | | POSTOP MONTH 6 | 189/291 (64%) | 85/291 (29%) | 14/291 (5%) | 6/291 (2%) | 0/291 (0%) | | | POSTOP MONTH 12 | 204/276 (74%) | 58/276 (21%) | 11/276 (4%) | 1/276 (0%) | 2/276 (1%) | | GLARE | SCREENING | 232/293 (79%) | 35/293 (12%) | 18/293 (6%) | 6/293 (2%) | 2/293 (1%) | | | POSTOP MONTH 6 | 227/291 (78%) | 59/291 (20%) | 5/291 (2%) | 0/291 (0%) | 0/291 (0%) | | | POSTOP MONTH 12 | 220/276 (80%) | 37/276 (13%) | 15/276 (5%) | 4/276 (1%) | 0/276 (0%) | | HALOS | SCREENING | 255/293 (88%) | 24/293 (8%) | 10/293 (3%) | 2/293 (1%) | 2/293 (1%) | | | POSTOP MONTH 6 | 235/291 (81%) | 42/291 (14%) | 10/291 (3%) | 4/291 (1%) | 0/291 (0%) | | | POSTOP MONTH 12 | 231/276 (84%) | 31/276 (11%) | 12/276 (4%) | 2/276 (1%) | 0/276 (0%) | | STARBURSTS | SCREENING | 271/293 (92%) | 14/293 (5%) | 6/293 (2%) | 2/293 (1%) | 0/293 (0%) | | | POSTOP MONTH 6 | 243/291 (84%) | 40/291 (14%) | 7/291 (2%) | 1/291 (0%) | 0/291 (0%) | | | POSTOP MONTH 12 | 243/276 (88%) | 21/276 (8%) | 11/276 (4%) | 1/276 (0%) | 0/276 (0%) | | DRYNESS^{3} | SCREENING | 222/293 (76%) | 57/293 (19%) | 8/293 (3%) | 4/293 (1%) | 2/293 (1%) | | | POSTOP MONTH 6 | 134/291 (46%) | 111/291 (38%) | 34/291 (12%) | 10/291 (3%) | 2/291 (1%) | | | POSTOP MONTH 12 | 153/276 (55%) | 92/276 (33%) | 18/276 (7%) | 9/276 (3%) | 4/276 (1%) | | PAIN | SCREENING | 290/293 (99%) | 2/293 (1%) | 1/293 (0%) | 0/293 (0%) | 0/293 (0%) | | | POSTOP MONTH 6 | 277/291 (95%) | 14/291 (5%) | 0/291 (0%) | 0/291 (0%) | 0/291 (0%) | | | POSTOP MONTH 12 | 269/276 (97%) | 4/276 (1%) | 2/276 (1%) | 0/276 (0%) | 1/276 (0%) | | FOREIGN BODY | SCREENING | 278/293 (95%) | 14/293 (5%) | 1/293 (0%) | 0/293 (0%) | 0/293 (0%) | | | POSTOP MONTH 6 | 238/291 (82%) | 47/291 (16%) | 6/291 (2%) | 0/291 (0%) | 0/291 (0%) | | | POSTOP MONTH 12 | 233/276 (84%) | 32/276 (12%) | 7/276 (3%) | 3/276 (1%) | 1/276 (0%) | $^{2}$ Clinically significant decrease (≥ 10% change) in the proportion of eyes reporting moderate to severe difficulty reading at 6 Months (17%) and 12 Months (21%) compared to baseline (32%). $^{3}$ Clinically significant increase (≥ 10% change) in the proportion of eyes reporting moderate to severe dry eye symptoms at 6 Months (16%) compared to baseline (5%). P970053/S009 SSED Page 34 of 36 41 {34} Changes in patient symptoms reported via a self-administered questionnaire are summarized below in Table 32. A patient's rating of a symptom was considered to be worse if there was 2 or more grade worsening in the symptom after LASIK compared to before LASIK, better if the change from baseline was 2 or more grades better after LASIK, and unchanged if there was only a one grade change or no change in the symptom after LASIK compared to baseline. Clinically significant changes in a symptom were considered to have occurred when there was a 10% or greater proportion of the subjects that reported an improvement (2 or more grades better than baseline) or worsening (2 or more grades worse than baseline) of a symptom. Using this criterion, there was a clinically significant improvement in night driving (12.4%) and difficulty reading (25.1%), and clinically significant worsening in dryness after LASIK (13.7%), as well as worsening of reading difficulty (10.3%), although this is offset by the number of patients with an improvement in their ability to read (25.1%). | TABLE 32 Change in Subjective Complaints between Baseline and 6 Months | | | | | --- | --- | --- | --- | | Symptom | Better than Baseline (2 or more grade change) | No Change from Baseline (0-1 grade change) | Worse than Baseline (2 or more grade change) | | LIGHT SENSITIVITY | 7.9% (23/291) | 89.3% (260/291) | 2.7% (8/291) | | DIFFICULT NIGHT DRIVING | 12.4% (36/291) | 85.2% (248/291) | 2.4% (7/291) | | DIFFICULTY READING | 25.1% (73/291) | 63.0% (186/291) | 10.3% (30/291) | | DOUBLE VISION | 0.7% (2/291) | 97.3% (283/291) | 2.1% (6/291) | | FLUCTUATION IN VISION | 1.4% (4/291) | 92.1% (268/291) | 6.5% (19/291) | | GLARE | 8.6% (25/291) | 90.0% (262/291) | 1.4% (4/291) | | HALOS | 3.4% (10/291) | 93.1% (271/291) | 3.4% (10/291) | | STARBURSTS | 2.1% (6/291) | 95.9% (279/291) | 2.1% (6/291) | |…