← Product Code [LZS](/productcode/LZS) · P970043S022

# LADARVISION 4000 EXCIMER LASER SYSTEM AND THE LADAR 6000 EXCIMER LASER SYSTEM (P970043S022)

_Alcon Laboratories · LZS · May 2, 2006 · Ophthalmic · APPR_

**Canonical URL:** https://fda-staging.innolitics.com/device/P970043S022

## Device Facts

- **Applicant:** Alcon Laboratories
- **Product Code:** [LZS](/productcode/LZS.md)
- **Decision Date:** May 2, 2006
- **Decision:** APPR
- **Device Class:** Class 3
- **Review Panel:** Ophthalmic
- **Attributes:** Therapeutic

## Indications for Use

The LADARVision®4000 and LADAR6000™ Excimer Laser Systems are indicated for wavefront-guided Laser Assisted In-Situ Keratomileusis (LASIK): - for the reduction or elimination of mixed astigmatism of 1.00D to less than 5.00D cycloplegic cylinder magnitude at the spectacle plane, which is greater than the sphere magnitude, and the cylinder and sphere have opposite signs; - in patients who are 21 years of age or older; and - in patients with documented stability of refraction for the prior 12 months, as demonstrated by a change in sphere and cylinder of less than or equal to 0.50D.

## Device Story

System uses wavefront measurement device (WMD) to map ocular aberrations (myopia, hyperopia, astigmatism, coma, spherical aberration) via Zernike polynomials; data exported to excimer laser system. Laser system uses Gaussian beam (<0.90mm diameter) and active closed-loop infrared eye-tracking (4000 Hz) to compensate for saccadic motion. Physician performs LASIK using microkeratome to create corneal flap; laser delivers spatially overlapping pulses to ablate cornea based on wavefront-guided profile. System includes motorized bed, plume removal, and microscope. Output is corrected corneal shape. Benefits include reduction/elimination of mixed astigmatism. Used in clinical settings by ophthalmologists. LADAR6000™ is functionally equivalent to LADARVision®4000 with minor ergonomic/illumination changes and higher repetition rate (92 Hz vs 60 Hz).

## Clinical Evidence

Prospective, non-randomized, multi-center clinical trial (110 eyes, 63 subjects). Primary endpoints: UCVA, predictability/stability of MRSE and cylinder, reduction of wavefront error, patient satisfaction. Results at 6 months: 98.2% UCVA 20/40 or better; 76.4% MRSE within 0.50D of intended; 89.1% cylinder magnitude <= 1.00D of intended. Total RMS wavefront error decreased by 67.2%. No loss of >2 lines BSCVA. Adverse events included miscreated flap (1.8%), epithelium in interface (5.4%), and DLK (4.5%).

## Technological Characteristics

Argon fluoride excimer laser (193 nm); 60-92 Hz repetition rate; 2.4-3.0 mJ pulse energy; <0.90mm beam diameter. Active closed-loop infrared (905 nm) eye-tracking. Wavefront-guided ablation based on Zernike polynomials. Connectivity via encrypted removable media. Standalone surgery planning software. Microkeratome required for flap creation.

## Reference Devices

- LADARVision® 4000 Excimer Laser System ([P970043](/device/P970043.md))
- LADAR6000™ Excimer Laser System ([P970043](/device/P970043.md)/S19)
- BD K-4000 microkeratome
- Hansatome microkeratome
- Moria CB and LSK microkeratomes

## Submission Summary (Full Text)

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Summary of Safety and Effectiveness

# SUMMARY OF SAFETY AND EFFECTIVENESS DATA

# 1. GENERAL INFORMATION

|  Device Generic Name: | Ophthalmic Excimer Laser System  |
| --- | --- |
|  Device Trade Name: | LADARVision®4000 Excimer Laser System and the LADAR6000™ Excimer Laser System  |
|  Applicant's Name and Address: | Alcon, Inc. 2501 Discovery Drive, Suite 500 Orlando, FL 32826  |
|  Date of Panel Recommendation: | None  |
|  Premarket Approval Application (PMA) Number: | P970043/S022  |
|  Date of Notice of Approval to Applicant: | May 2, 2006  |

The LADARVision®4000 Excimer Laser System was approved on November 2, 1998 for the indication of photorefractive keratectomy (PRK) for the reduction or elimination of mild to moderate myopia of between -1.00 and -10.00D sphere and less than or equal to -4.00D astigmatism at the spectacle plane, the combination of which must result in an attempted correction of between -0.50D and -10.00D spherical equivalent (SE) at the spectacle plane where the sphere or cylinder is at least 1.00D (P970043). On May 9, 2000, the device was approved for the indication of laser in-situ keratomileusis (LASIK) for the reduction or elimination of myopia of less than -9.00D sphere and -0.50D to less than -3.00D astigmatism at the spectacle plane (P970043/S5). On September 22, 2000, the device was approved for the indication of LASIK for the reduction or elimination of refractive error of less than or equal to +6.00D sphere and -6.00D astigmatism at the spectacle plane (hyperopia with or without astigmatism and mixed astigmatism) (P970043/S7).

On October 18, 2002, the LADARVision®4000 System was approved for wavefront-guided LASIK for the reduction or elimination of myopia up to -7.00D sphere with less than -0.50D astigmatism at the spectacle plane (P970043/S10). On June 29, 2004, the device was approved for wavefront-guided LASIK for the reduction or elimination of myopic astigmatism up to -8.00D sphere with -0.50D to -4.00D cylinder and up to -8.00D spherical equivalent at the spectacle plane (P970043/S15). On May 26, 2005, the sponsor submitted a supplement for wavefront-guided LASIK for the reduction or elimination of hyperopia and hyperopic astigmatism of +0.75D to less than +5.00D sphere with up to -3.00D cylinder and up to +5.00D spherical equivalent (SE) at the spectacle plane (P970043/S020).

The LADAR6000™ Excimer Laser System was approved on May 1, 2006 in P970043/S19. Because this laser was found comparable to the LADARVision® 4000 Excimer Laser System based on preclinical and testing data, approval of this supplement (S22) allows the use of both laser systems for the mixed astigmatism indication.

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On May 1, 2006, FDA issued an approval order for PMA P970043/S23 for an increase in the laser repetition rate from 60 Hz to 92 Hz in the LADAR6000™ Excimer Laser System.

The sponsor submitted this supplement to further expand the clinical indications to include wavefront-guided CustomCornea® LASIK for mixed astigmatism. The updated clinical data to support the expanded indication is provided in this summary. The pre-clinical test results were provided in the original PMA and prior PMA supplements. 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 #02M-0487 or you may download these files from the internet site http://www.fda.gov/cdrh/pdf/p970043.pdf.

## II. INDICATIONS FOR USE

The LADARVision®4000 and LADAR6000™ Excimer Laser Systems are indicated for wavefront-guided Laser Assisted In-Situ Keratomileusis (LASIK):

- for the reduction or elimination of mixed astigmatism of 1.00D to less than 5.00D cycloplegic cylinder magnitude at the spectacle plane, which is greater than the sphere magnitude, and the cylinder and sphere have opposite signs;
- in patients who are 21 years of age or older; and
- in patients with documented stability of refraction for the prior 12 months, as demonstrated by a change in sphere and cylinder of less than or equal to 0.50D.

### III. CONTRAINDICATIONS

Wavefront-guided LASIK is contraindicated in:

- pregnant or nursing women.
- patients with autoimmune, collagen vascular, or immunodeficiency diseases.
- patients with signs of keratoconus.
- patients who are taking one or both of the following medications: isotretinoin (Accutane¹) or amiodarone hydrochloride (Cordarone²).

### IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the device labeling.

### V. DEVICE DESCRIPTION

A. Wavefront Measurement Device (WMD)

The first step in performing CustomCornea® LASIK surgery is to perform a wavefront examination on the patient using a wavefront measurement device (WMD) compatible with the LADARVision®4000 and the LADAR6000™ Excimer Laser Systems. At the present time, the only compatible WMD is the Alcon®

¹ Accutane Reg. TM of Hoffman-La Roche Inc.

² Cordarone Reg. TM of Sanofi-Synthelabo Inc.

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LADARWave® CustomCornea® Wavefront System, the wavefront measurement device used in the clinical trial.

The LADARWave® CustomCornea® Wavefront System is indicated for measuring, recording, and analyzing visual aberrations (such as myopia, hyperopia, astigmatism, coma and spherical aberration) and for displaying refractive error maps of the eye to assist in prescribing refractive corrections. This device is enabled to export wavefront data and associated anatomical registration information to a compatible treatment laser with an indication for wavefront-guided refractive surgery.

Essential features of the compatible WMD are as follows:

1. Patient Fixation and Fogging

The WMD includes a fixation optical subsystem that provides the patient with an unambiguous fixation point. In addition, the fixation subsystem includes adjustable optics to compensate for the patient's inherent refractive error. The optics are used to "fog" the eye, first clarifying the fixation target and then it optically adjusts beyond the patient's far point to minimize accommodation.

2. Centration

Prior to dilation, the WMD is used to record the geometric relationship between the natural daytime pupil center and the limbus of the eye. This information is then used to center the wavefront measurement and subsequent ablative treatment on the natural line of sight.

3. Wavefront Measurement

The WMD measures the wavefront profile of the eye with a high degree of accuracy and characterizes the profile using Zernike polynomials. The pupil must be large enough so that valid wavefront data can be obtained over a large area. Higher-order aberrations are more significant at night when the pupil is naturally larger. Therefore, when treating these aberrations, measurement over a large pupil provides the greatest utility.

4. Registration

The WMD uses synchronized video imagery and on-screen software reticules to record the relationship of the wavefront data to the limbus of the eye and to ink marks applied to the sclera just before the wavefront exam. This registration information is used to position the excimer ablation profile at the correct corneal location and cyclotorsional angle.

5. Data Export

The WMD has the ability to export the wavefront examination data as an electronic file to removable media for transfer to the LADARVision®4000 and LADAR6000™ Systems. The electronic file is structured in a specific format and contains essential patient information, centration/registration information, and the detailed aberration data. In addition, the electronic file is encrypted in a manner that can only be deciphered by the LADARVision®4000 and LADAR6000™ Systems.

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# B. Microkeratome

The LASIK procedure requires the use of a commercially available microkeratome that has been cleared for marketing via a premarket notification. The device used in this study consists of a head, plates, ring, handle, wrenches, shaft, motor, hand-piece, disposable blades, and power supply with footswitches and power cords. The system is completed with the applanation lens set, tonometer, corneal storage jar, optical zone marker, spatula, stop attachment, and digital thickness gauge.

The microkeratomes used in the clinical trial included the BD K-4000³ (manufactured by Becton-Dickinson), Hansatome⁴ (manufactured by Bausch & Lomb), and the Moria⁵ CB and LSK (manufactured by Moria).

# C. CustomCornea® Surgery Planning Software

The CustomCornea® Surgery Planning Software is a stand-alone computer application linking the diagnostic wavefront data with the surgical treatment on the LADARVision®4000 and LADAR6000™ Excimer Laser Systems. The planning software allows refinement of surgical parameters within the approved wavefront-guided indication for the LADARVision®4000 and LADAR6000™ Systems, and calculation of ablation depth.

System, calculates ablation depth, checks for treatment eligibility, and exports all messages and warnings to the excimer laser system.

After completing the surgery planning tasks, the planned treatment file is transferred to the LADARVision®4000 and LADAR6000™ Systems. The LADARVision®4000 and LADAR6000™ Systems software imports the treatment file, calculates the excimer treatment pattern, and performs the surgery.

Software version 1.0 was used in the clinical trial. Software version 1.4 is the commercial release version.

# D. LADARVision®4000 Excimer Laser System

The LADARVision®4000 excimer laser beam is of Gaussian profile and small in diameter (<0.90mm). Corneal sculpting is achieved by delivering hundreds to thousands of excimer laser pulses to the eye in a complex pattern of spatially overlapping spots, and precision of this process depends on accurate placement of the laser pulses. The LADARVision®4000 Excimer Laser System incorporates the LADARTracker® closed-loop eye-tracking system to track and compensate for patient eye motion, including saccadic movements, during procedures so that each excimer laser pulse is delivered to the appropriate location on the cornea.

Rather than the refractive correction being entered manually by the physician based on phoropter refraction, the CustomCornea® treatment requires that the pre-operative aberrations in the eye be measured with a wavefront measurement device. The treatment is based on Zernike data derived from a wavefront measurement device.

³ BD K-4000 TM of Becton, Dickinson and Company

⁴ Hansatome Reg. TM of Bausch & Lomb Incorporated

⁵ Moria Reg. TM of Moria SA

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including treatment of lower-order sphere and astigmatism components and higher-order components, such as coma and spherical aberration.

The electronic file that the LADARVision®4000 System receives from the wavefront measurement device includes the following information:

- Patient information, including name, identification number, and clinical prescription.
- Eye information, including OD/OS and the geometric relationship of the wavefront data to the limbus and to the pupil center.
- Wavefront information, including a Zernike polynomial representation of the wavefront and the physical radius of that description.

The excimer laser beam characteristics (i.e., pulse energy, firing rate, fluence distribution at the treatment plane) are the same for Conventional and CustomCornea® treatment modalities. The Conventional LADARVision®4000 System treatment utilizes sphere, cylinder and axis components entered manually by the operator to generate the ablation profile. The CustomCornea® LASIK shaping algorithm utilizes aberration information unique to a given eye that is obtained from the WMD to guide the ablation of the cornea. The wavefront information is registered to the anatomical geometry of the eye using the WMD while the patient is sitting upright. This registered alignment information is passed to the LADARVision®4000 System, which allows for the compensation of this alignment information due to the natural cyclotorsion incurred when the patient assumes a prone position and uses the geometry information to accurately position the customized ablation profile on the eye.

The approved CustomCornea® ablation zone parameters, as used in the clinical trial, include a 6.5mm optical zone with a 1.25mm blend zone for a 9.0mm total ablation zone.

CustomCornea® mixed astigmatism corrections are locked out for greater than 6.00D cycloplegic cylinder magnitude. A flag warning will appear when a correction above the approved indication is selected.

Features and components of the LADARVision®4000 Excimer Laser System include:

# 1. Excimer laser

This argon fluoride excimer laser produces 10 nanosecond pulses of ultraviolet radiation at a wavelength of 193 nanometers. The laser repetition rate is approximately 60 pulses per second for the LADARVision®4000 Excimer Laser System and approximately 92 pulses per second for the LADAR6000™ System. The characteristics of the laser beam at the corneal treatment plane include: a pulse energy of 2.4 to 3.0mJ; a beam diameter of less than 0.90mm; and average fluence of 180 to 240 mJ/cm².

# 2. Optical transmission system

The excimer laser passes through an optical telescope, followed by reflection off a series of mirrors, which position the excimer laser pulses in the correct locations at the treatment plane.

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# 3. Energy monitoring and control

The laser pulse energy is monitored to ensure delivery of 2.4 to 3.0 mJ to the eye prior to surgery and during ablation.

# 4. Gas handling system

The excimer laser enclosure holds the laser, gas bottle, and gas-plumbing manifold. The gas bottle contains the pre-mixed gas, including argon, fluorine, and neon as the buffer gas. Gas flow is regulated through the system, responding to commands from the laser control electronics board.

# 5. Active Closed-Loop Eye Tracking System

The LADARTracker® System actively tracks the position of the eye by irradiating it with pulses of 905 nm infrared "eye-safe" energy and analyzing characteristics of the returning laser radiation. This measurement occurs 4000 times each second to detect even rapid eye motion before significant movement of the cornea has occurred. The LADARTracker® System actively compensates for the detected motion, rather than simply disabling the laser when the eye position exceeds some tolerated error range.

# 6. Operating microscope

The stereo viewing operating microscope is located in the optics head. The dual optical paths are independent of the excimer beam path and the tracker mirrors.

# 7. Fixation target

A visible fixation target is mounted in the system to facilitate the patient looking in the direction of the excimer beam. The fixation target consists of a light emitting diode (LED), a pinhole aperture, an edge-illuminated reticule, and a lens.

# 8. Motorized Bed and Cross Beam Patient Positioning

A motorized patient bed, which moves on X, Y and Z axes, smoothly and rapidly positions the patient and facilitates bilateral procedures. Cross beam Class I lasers are used to place the cornea at a predetermined height for proper ablation.

# 9. Plume Removal System

The plume removal system is housed within the calibration stage. During surgery, the plume removal system is deployed to a pre-determined height and provides a constant level of plume removal during ablation.

# 10. System Software Control

The LADARVision®4000 System software enables the user to: properly center the treatment; make adjustments in the X and Y axes; adjust for cyclotorsion and correctly reference astigmatism; place a hinge guard to protect the flap during surgery; and properly match the alignment of the wavefront map to the ablation.

Software versions 5.09, 5.11, 5.13 and 5.13 (Build 7) were used in the clinical trial for the Primary Cohort. Software version 5.4 is the commercial release version.

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# E. LADAR6000™ Excimer Laser System

The LADAR6000™ Excimer Laser System was approved on May 1, 2006. The LADAR6000™ laser is functionally equivalent to the LADARVision® 4000 in that:

1. The excimer laser engine has not changed;
2. The excimer laser beam characteristics at the eye plane are unchanged;
3. Infrared LADAR eye tracking remains unchanged;
4. The shot pattern algorithms are unchanged (for a given treatment, identical shot patterns are generated and the sequence and timing of these shots are identical); and,
5. Treatment procedures are the same.

The differences between the two laser systems are:

1. Design changes in the LADAR6000™ Illumination System (2 new light sources for illumination during surgery: one to improve visualization of blood vessels, and the other to improve visualization of the pupil-iris boundary);
2. Tighter calibration controls to the LADAR6000™ with the addition of a software parameter to establish and monitor a Volume-Per-Shot (VPS) band to ensure the laser energy is within the acceptable energy levels;
3. Changes to the device labeling (name change to LADAR6000™); and,
4. Modifications to the user interface in the LADAR6000™ System Operation Manual.

The LADAR6000™ Excimer Laser System had only minor ergonomic and obsolescence changes to the LADARVision® 4000 Excimer Laser System. Additionally, an increase in the laser repetition rate from 60 Hz to 92 Hz was approved on May 1, 2006 for just the LADAR6000™ Excimer Laser System. All specs for beam shape, fluence, and wavelength were unchanged in the LADAR6000™. The shot pattern, algorithms, and frequency of operation were unchanged. The design changes were illumination and ergonomic features that affected some labeling. The complete system had validation and verification testing. Based on engineering reviews of this application, the use of the LADAR6000™ Excimer Laser System should not introduce any new safety or effectiveness problems regarding wavefront-guided LASIK treatment of mixed astigmatism. Therefore, the LADAR6000™ Excimer Laser System is considered comparable to the LADARVision® 4000 Excimer Laser System for this indication for use, and PMA approval includes both models.

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are currently several other alternatives for the correction of mixed astigmatism:

Automated Lamellar Keratoplasty (ALK)

Contact Lenses

Conventional Laser Assisted In-Situ Keratomileusis (LASIK)-based on phoropter refraction
Radial Keratotomy (RK)

Spectacles

Each alternative has its own advantages and disadvantages. A prospective patient should fully discuss with his/her care provider these alternatives in order to select the correction method that best meets his/her expectation and lifestyle.

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### VII. MARKETING HISTORY

The LADARVision®4000 and LADAR6000™ Excimer Laser Systems have been marketed in the following countries: Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, Cyprus, Czech Republic, France, Germany, Greece, Hong Kong, India, Italy, Korea, Malaysia, Mexico, Netherlands, Norway, Peru, Philippines, Portugal, Puerto Rico, Singapore, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States, and Vietnam. The LADARVision®4000 and LADAR6000™ Excimer Laser Systems have not been withdrawn from marketing for any reason relating to the safety and effectiveness of the device.

### VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Potential adverse effects associated with LASIK include: loss of best spectacle corrected visual acuity (BSCVA); worsening of patient complaints such as double vision, sensitivity to bright lights, increased difficulty with night vision, fluctuations in vision; increase in intraocular pressure; corneal haze; secondary surgical intervention; corneal infiltrate or ulcer; corneal epithelial defect; corneal edema; problems associated with the flap including a lost, misplaced or misaligned flap; retinal detachment; and retinal vascular accidents.

Refer to Section X.F.2.e (Safety Outcomes) for a complete listing of adverse events and complications observed during the clinical study.

### IX. SUMMARY OF PRECLINICAL STUDIES

A series of pre-clinical tests were conducted upon initial development for conventional refractive surgery procedures prior to entry into human clinical trials. Those tests included algorithm simulations and ablation profiles using plastic blocks, as well as animal testing. Please refer to the SSED for the original PMA (P970043) for a summary of the pre-clinical testing.

A series of pre-clinical tests were conducted on the CustomCornea® algorithms prior to entering human clinical trials. These tests included algorithm validation, which tested the ablation shot pattern in both an ablation simulation program and actual PMMA substrate (surrogate) ablation experiments. Excellent agreement was demonstrated between the results obtained from PMMA substrate and simulated ablations. The CustomCornea® algorithm reproduced the results obtained with the existing conventional algorithm and demonstrated accuracy in performing more complex ablations. This algorithm validation provided sufficient evidence to proceed to human clinical trials.

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# X. SUMMARY OF CLINICAL STUDIES

The Sponsor performed a clinical study of wavefront-guided CustomCornea® LASIK correction of mixed astigmatism using the LADARVision®4000 System in the U.S. under an investigational device exemption application (IDE G950213). In addition, one foreign site collected data under an investigational device application in Canada using a protocol that was the same as the U.S. protocol in terms of the inclusion and exclusion criteria, study procedures, patient measurements, and the treatment applied to the eye. Therefore, data from the U.S. and Canadian centers were pooled for the analysis of safety and effectiveness. A summary of the clinical trial is presented below.

# A. Study Objective

The primary objective of the clinical investigation of the LADARVision®4000 Excimer Laser System for wavefront-guided CustomCornea® LASIK correction of mixed astigmatism was to establish safety and effectiveness. Secondary study objectives included 1) to obtain preoperative and postoperative wavefront data to aid in the understanding of refractive and corneal shape changes as a result of the surgery and postoperative healing; and 2) to analyze the relationship between quality of vision indicators calculated from the wavefront data and clinical outcomes.

# B. Study Design

The initial study design in the U.S. protocol began as a prospective, randomized, unmasked multi-center trial, where one eye of each patient was randomly assigned CustomCornea® treatment based on data from the wavefront system and the fellow eye was assigned conventional treatment based on cycloplegic phoropter refraction. For this initial subgroup of patients, the fellow eye served as a contralateral control.

The U.S. study was changed to a prospective, non-randomized, unmasked, multi-center trial, where one or both eyes of a patient received wavefront-guided CustomCornea® treatment. An equivalent study design was also in progress under a Canadian protocol. In this case, the primary control was the preoperative state of the treated eye for comparison with postoperative outcomes.

# C. Inclusion and Exclusion Criteria

Recruited patients had the study details and follow-up requirements explained to them and were asked to sign an Informed Consent Document preoperatively. To be eligible for the study, mixed astigmatic patients must have had a preoperative cycloplegic refraction at the spectacle plane of > 0.00D to +6.00D sphere with < 0.00D to -6.00D astigmatism (in minus cylinder convention) with an absolute cylinder magnitude greater than the sphere magnitude. Enrollment of mixed astigmatic eyes in the study occurred over the preoperative cycloplegic refractive range of +0.25D to +4.25D sphere with -1.00D to -6.00D astigmatism and -1.38D to +1.63D spherical equivalent (SE).

Stability of refraction must have been established and documented using previous clinical records or measurement of spectacles. Stability was demonstrated by a change in the manifest sphere and cylinder over the prior 12 months of less than or equal to 0.50D. If a year-old refraction was not available, the change in refraction

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must have been 0.50D or less per year since the last documented refraction in both the manifest sphere and cylinder to a 1.00D maximum SE change. The manifest and cycloplegic refraction measured at the preoperative examination must have been within 1.00D of each other in the sphere and cylinder components. In addition, the cycloplegic refraction could not differ by more than 1.00D in sphere or cylinder from the attempted correction determined by the wavefront system.

For the contralateral treatment group, the cycloplegic refraction between the patient's two eyes could not differ by more than 1.00D in sphere or cylinder. In addition, patients must have been willing to have LASIK correction in both eyes within a 2-week period. These two criteria were not applicable to patients treated under the bilateral CustomCornea® treatment study design.

Patients must have been at least 18 years of age and had a BSCVA of 20/25 or better in the operative eye(s). Patients must have been willing to return for scheduled follow-up examinations for 9 months after surgery and have their eyes pharmacologically dilated at the required visits.

Patients who were contact lens wearers were requested to discontinue contact lens wear for a minimum of 2 weeks for soft contact lenses and 3 weeks for hard contact lenses (RGP/PMMA) prior to the preoperative examination. Patients who had previously worn hard lenses were required to have two examinations conducted 2 to 3 weeks apart to show stability of refraction without lens wear. Prior to surgery, patients were not to wear their contact lenses in the operative eye(s) for 2 to 3 weeks for soft and hard contact lenses, respectively.

Patients who exhibited any of the following conditions were excluded from the study:

- previous corneal, intraocular, or strabismus surgery in the operative eye(s)
- history of active clinically significant or visually threatening ocular disease or pathology
- clinically significant corneal scar within the ablation zone or other corneal abnormality such as recurrent erosion or severe basement membrane disease
- signs of keratoconus
- irregular corneal astigmatism
- history of herpes keratitis
- autoimmune disease, connective tissue disease, clinically significant atopic syndrome or diabetes
- use of chronic systemic corticosteroids or other immunosuppressive therapy
- use of systemic medication with significant ocular side effects
- pregnant or lactating females
- use of ophthalmic medications other than artificial tears for treatment of an ocular pathology
- severe dry eye syndrome unresolved by treatment
- known allergy to study medications
- glaucoma or glaucoma filtering surgery
- participation in another ophthalmic clinical trial
- calculated residual posterior stromal thickness of less than 250 microns
- unable to achieve a pupillary dilation of ≥7mm
- at risk for angle closure

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- an inability to obtain a clear and complete wavefront image

D. Study Plan, Patient Assessments, and Effectiveness Criteria

All patients were expected to return for follow-up at 1 day, 1 week, and 1, 3, 6 and 9 months postoperatively. All CustomCornea® treatments in the study were conducted using an optical zone of 6.5mm with a blend zone of 1.25mm for a total ablation zone of 9.0mm. All eyes were required to be treated for a target of emmetropia. All surgeries performed in the study were subject to approval by the Sponsor.

Under the contralateral treatment study design, patients were required to have their fellow eye treated with Conventional LASIK on the same day or within 2 weeks of the CustomCornea® treatment in the primary eye.

Under the bilateral CustomCornea® treatment study design, patients were permitted to have the fellow eye treated on the same day as the primary eye or any time thereafter provided there was no active complication or adverse event for the primary eye.

Retreatments were permitted after the 3-month follow-up visit based on these criteria:

1. An uncorrected visual acuity (UCVA) worse than 20/25 or residual sphere or cylinder greater than or equal to 0.50D at both of the two most recent consecutive visits that are at least one month apart.
2. Stable refraction with the sphere and cylinder components within 0.50D on two most recent consecutive visits that are at least one month apart.
3. Stable UCVA (i.e., within one line) on two consecutive visits at least one month apart.
4. Patient's signature on a separate Retreatment Informed Consent document, wherein the patient is informed of the risks associated with retreatment.
5. The eligibility criteria are met and an ophthalmic evaluation (including visual acuity, manifest refraction, and slit lamp) is done to establish the preoperative condition of the eye.
6. Prior written approval from the Sponsor of the study.

Retreatment for the purpose of correcting residual refractive error was not considered a treatment failure. Retreated patients were exited from the study and re-entered as a retreatment case. Results of retreated eyes were analyzed separately from the primary treatment population.

No other ocular surgery procedures were allowed unless deemed medically necessary by the Investigator. The Investigator was required to notify the Sponsor prior to any secondary surgical intervention, except in the case of an emergency in which case notification must occur as soon as possible.

In the event of a miscreated flap with the microkeratome, considered an adverse event in the study, a second cut with the microkeratome with completion of the laser ablation procedure was allowed after a minimum of 3 months. Approval from the Medical Monitor was required prior to treating an eye with a miscreated flap.

Preoperatively, the patient's medical and ocular histories were recorded. The objective parameters measured during the study included: uncorrected visual acuity, best spectacle corrected visual acuity, pupil size, vertex distance, manifest and

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cycloplegic refraction, wavefront measurement, contrast sensitivity, intraocular pressure, angle assessment, slit lamp and dilated fundus examination.

The following objective parameters were collected preoperatively and only as needed postoperatively: corneal thickness, corneal topography, and keratometry. The subjective parameters measured during the study included a patient questionnaire.

The primary effectiveness parameters for this study were: improvement of UCVA; predictability and stability of manifest refraction spherical equivalent (MRSE) and manifest cylinder; reduction of wavefront error, including higher-order aberrations; and patient satisfaction. The safety parameters were: preservation of BSCVA; absence of significant findings in slit lamp and fundus examination; absence of significant intraocular pressure (IOP) elevation; and incidence of complications and adverse events.

# E. Study Period, Investigational Sites, and Demographics

# 1. Study Period and Investigational Sites

The Primary Cohort enrollment of 110 eyes of 63 subjects in the CustomCornea® wavefront-guided mixed astigmatism LASIK study occurred between December 11, 2002 and December 28, 2004. All eyes were treated based on the Zernike data from the wavefront measurement system including lower-order aberrations, such as sphere and cylinder and higher-order aberrations, such as spherical aberration and coma. Nine investigational sites enrolled patients in the Primary Cohort, including eight U.S. sites and one Canadian site.

# 2. Demographics

The demographics of the study population (Table 1) were typical for a refractive surgery trial performed in the U.S. The mean ± standard deviation patient age was 40.6 ± 10.7 years with a range from 20 to 60 years. The majority of patients were Caucasian (94.5%) and the remaining patients were Hispanic (3.6%) and Indian (1.8%). Slightly more females (53.6%) than males (46.4%) participated in the study. The distribution of right and left eyes that received treatment was approximately equal (49.1% vs. 50.9%). While most patients (64.5%) did not wear contact lenses prior to surgery, 32.7% wore soft contact lenses and 2.7% wore rigid gas permeable (RGP) lenses. Preoperative patient characteristics that were found to associate with outcomes are discussed in Section X.F.2.j. (Statistical Analysis Outcomes).

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|  Table 1. Demographics  |   |   |
| --- | --- | --- |
|  110 Eyes of 63 Enrolled Patients  |   |   |
|  Age (In Years) Average ± Standard Deviation Minimum to Maximum | 40.6 ± 10.7 20 to 60  |   |
|  Race | N | % Eyes  |
|  Caucasian | 104 | 94.5%  |
|  Hispanic | 4 | 3.6%  |
|  Indian | 2 | 1.8%  |
|  Gender | Female | 59 53.6%  |
|  Male | 51 | 46.4%  |
|  Eye | Left | 56 50.9%  |
|  Right | 54 | 49.1%  |
|  Contact Lens History | None | 71 64.5%  |
|  Soft | 36 | 32.7%  |
|  Rigid Gas Permeable (RGP) | 3 | 2.7%  |

# F. Data Analysis and Results

# 1. Preoperative Characteristics

The study population of mixed astigmatic eyes had a preoperative cycloplegic cylinder magnitude greater than the sphere in minus cylinder convention. Preoperative cycloplegic refractive range was +0.25D to +4.25D sphere with -1.00D to -6.00D cylinder and -1.38D to +1.63D spherical equivalent. The mean ± standard deviation for the preoperative cycloplegic refraction was +1.50D ± 0.94D sphere, -2.90D ± 1.20D cylinder and +0.06D ± 0.65D spherical equivalent. Table 2 displays the number of eyes stratified by preoperative cycloplegic sphere and cylinder. Table 3 displays the number of eyes stratified by preoperative cycloplegic spherical equivalent and cylinder.

|  Table 2. Preoperative Cycloplegic Refraction Stratified by Sphere and Cylinder  |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  CYLINDER MAGNITUDE (D) IN MINUS CYLINDER CONVENTION  |   |   |   |   |   |   |   |
|  SPHERE (D) |   | -1.00 to -1.99 | -2.00 to -2.99 | -3.00 to -3.99 | -4.00 to -4.99 | -5.00 to -6.00 | TOTAL  |
|  > 0.00 to +0.99 | n/N | 15/110 | 14/110 | 7/110 | 0/110 | 0/110 | 36/110  |
|   |  % | 13.6% | 12.7% | 6.4% | 0.0% | 0.0% | 32.7%  |
|  +1.00 to +1.99 | n/N | 9/110 | 19/110 | 10/110 | 3/110 | 0/110 | 41/110  |
|   |  % | 8.2% | 17.3% | 9.1% | 2.7% | 0.0% | 37.3%  |
|  +2.00 to +2.99 | n/N | 0/110 | 4/110 | 6/110 | 9/110 | 4/110 | 23/110  |
|   |  % | 0.0% | 3.6% | 5.5% | 8.2% | 3.6% | 20.9%  |
|  +3.00 to +3.99 | n/N | 0/110 | 0/110 | 2/110 | 5/110 | 2/110 | 9/110  |
|   |  % | 0.0% | 0.0% | 1.8% | 4.5% | 1.8% | 8.2%  |
|  +4.00 to +5.00 | n/N | 0/110 | 0/110 | 0/110 | 0/110 | 1/110 | 1/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.9% | 0.9%  |
|  TOTAL | n/N | 24/110 | 37/110 | 25/110 | 17/110 | 7/110 | 110/110  |
|   |  % | 21.8% | 33.6% | 22.7% | 15.5% | 6.4% | 100.0%  |

D = Diopter

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|  Table 3. Preoperative Cycloplegic Refraction Stratified by Spherical Equivalent and Cylinder  |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  CYLINDER MAGNITUDE (D) IN MINUS CYLINDER CONVENTION  |   |   |   |   |   |   |   |
|  SPHERICAL EQUIVALENT (D) |   | -1.00 to -1.99 | -2.00 to -2.99 | -3.00 to -3.99 | -4.00 to -4.99 | -5.00 to -6.00 | TOTAL  |
|  -1.00 to -2.00 | n/N | 0/110 | 1/110 | 5/110 | 2/110 | 0/110 | 8/110  |
|   |  % | 0.0% | 0.9% | 4.5% | 1.8% | 0.0% | 7.3%  |
|  0.00 to -0.99 | n/N | 9/110 | 19/110 | 11/110 | 3/110 | 3/110 | 45/110  |
|   |  % | 8.2% | 17.3% | 10.0% | 2.7% | 2.7% | 40.9%  |
|  +0.01 to +0.99 | n/N | 15/110 | 15/110 | 4/110 | 9/110 | 2/110 | 45/110  |
|   |  % | 13.6% | 13.6% | 3.6% | 8.2% | 1.8% | 40.9%  |
|  +1.00 to +2.00 | n/N | 0/110 | 2/110 | 5/110 | 3/110 | 2/110 | 12/110  |
|   |  % | 0.0% | 1.8% | 4.5% | 2.7% | 1.8% | 10.9%  |
|  TOTAL | n/N | 24/110 | 37/110 | 25/110 | 17/110 | 7/110 | 110/110  |
|   |  % | 21.8% | 33.6% | 22.7% | 15.5% | 6.4% | 100.0%  |

(D) = Diopter

# 2. Postoperative Results

# a. Accountability

Accountability for this study was ≥ 98.2% at all postoperative intervals (Table 4). Postoperative data were available for 110 eyes (100%) up to 6 months and for 108 eyes (98.2%) at 9 months. One patient (2 eyes) missed the 9-month visit because the patient moved out of the country prior to the opening of the 9-month visit window.

|  Table 4. Accountability at Each Visit  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |  | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  Total Eyes Enrolled | N | 110 | 110 | 110 | 110  |
|  Available for Analysis | N | 110 | 110 | 110 | 108  |
|   |  % | 100.0% | 100.0% | 100.0% | 98.2%  |
|  Unavailable Missed Visit | N | 0 | 0 | 0 | 2  |
|   |  % | 0.0% | 0.0% | 0.0% | 1.8%  |
|  % Accountability= [available/(available + unavailable)] | % | 100.0% | 100.0% | 100.0% | 98.2%  |

# b. Stability of Outcome

Refractive stability was analyzed as paired differences in the non-vector manifest cylinder magnitude between consecutive visits (Table 5). Eyes with data available at each postoperative interval were evaluated in a 6-month consistent cohort of 110 eyes and a 9-month cohort of 108 eyes.

Cylinder stability was achieved between 1 and 3 months with 100% of eyes demonstrating ≤ 1.00D magnitude change and a mean change of -0.05D ± 0.29D at a rate of -0.03D change per month for the 6-month consistent cohort. Cylinder stability was confirmed between 3 and 6 months with 100%

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of eyes demonstrating ≤ 1.00D magnitude change and a decrease in the mean change over time to 0.02D ± 0.24D at a rate of 0.01D change per month. The 95% confidence interval of the mean change in cylinder magnitude overlapped between postoperative intervals with a narrow range (≤ 0.11D) between the upper and lower limits.

The 9-month consistent cohort supported the overall trends in cylinder stability observed among the 6-month cohort. Between all consecutive postoperative intervals, at least 99.1% of eyes showed ≤ 1.00D of cylinder magnitude change. The mean change in cylinder magnitude was 0.05D ± 0.25D between 6 and 9 months at a rate of 0.02D change per month.

|  **Table 5. Stability of Manifest Cylinder Magnitude**  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  **6-Month Cohort** (N=110) | **Change in Cylinder Magnitude Between** |   | **1 and 3 Months** | **3 and 6 Months** |   |
|   |  ≤ 1.00D | n/N % | 110/110 100.0% | 110/110 100.0% |   |
|   |  Mean Change* ± Standard Deviation |   | -0.05 ± 0.29 | 0.02 ± 0.24  |   |
|   |  95% Confidence Interval of Mean Change |   | (-0.11, 0.00) | (-0.03, 0.06)  |   |
|   |  Mean Change* per Month |   | -0.03 | 0.01  |   |
|  **9-Month Cohort** (N=108) | **Change in Cylinder Magnitude Between** |   | **1 and 3 Months** | **3 and 6 Months** | **6 and 9 Months**  |
|   |  ≤ 1.00D | n/N % | 108/108 100.0% | 108/108 100.0% | 107/108 99.1%  |
|   |  Mean Change* ± Standard Deviation |   | -0.05 ± 0.29 | 0.01 ± 0.23 | 0.05 ± 0.25  |
|   |  95% Confidence Interval of Mean Change |   | (-0.11, 0.00) | (-0.03, 0.05) | (0.00, 0.10)  |
|   |  Mean Change* per Month |   | -0.03 | 0.003 | 0.02  |

D = Diopter

* Positive value reflects an increase in magnitude and a negative value reflects a decrease in magnitude between visits.

Similarly, refractive stability was analyzed as paired differences in MRSE between consecutive visits for the 6-month and 9-month consistent cohorts of eyes with data available at each postoperative interval (Table 6).

Stability of MRSE was achieved between 1 and 3 months with 100% of eyes demonstrating a change in MRSE ≤ 1.00D and a mean change of 0.06D ± 0.29D at a rate of 0.03D change per month for the 6-month consistent cohort. Stability was confirmed between 3 and 6 months with 100% of eyes demonstrating a change in MRSE ≤ 1.00D and a decrease in the mean change over time to 0.03D ± 0.25D at a rate of 0.01D change per month. The 95% confidence interval of the mean change in MRSE overlapped between postoperative intervals with a narrow range (≤ 0.11D) between the upper and lower limits.

The 9-month consistent cohort showed similar MRSE stability trends to the 6-month cohort. All eyes demonstrated a change in MRSE ≤ 1.00D between postoperative visits. Between 6 and 9 months, the mean MRSE change was -0.04D ± 0.26D at a rate of -0.01D change per month.

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|  Table 6. Stability of Manifest Refraction Spherical Equivalent  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  6-Month Cohort (N=110) | Change in MRSE Between |   | 1 and 3 Months | 3 and 6 Months |   |
|   |  ≤ 1.00D | n/N % | 110/110 100.0% | 110/110 100.0% |   |
|   |  Mean Change ± Standard Deviation |   | 0.06 ± 0.29 | 0.03 ± 0.25  |   |
|   |  95% Confidence Interval of Mean Change |   | (0.00, 0.11) | (-0.01, 0.08)  |   |
|   |  Mean Change per Month |   | 0.03 | 0.01  |   |
|  9-Month Cohort (N=108) | Change in MRSE Between |   | 1 and 3 Months | 3 and 6 Months | 6 and 9 Months  |
|   |  ≤ 1.00D | n/N % | 108/108 100.0% | 108/108 100.0% | 108/108 100.0%  |
|   |  Mean Change ± Standard Deviation |   | 0.06 ± 0.29 | 0.03 ± 0.25 | -0.04 ± 0.26  |
|   |  95% Confidence Interval of Mean Change |   | (0.00, 0.11) | (-0.02, 0.07) | (-0.09, 0.01)  |
|   |  Mean Change per Month |   | 0.03 | 0.01 | -0.01  |

D = Diopter

# c. Effectiveness Outcomes

The key effectiveness outcomes for UCVA and accuracy of MRSE and manifest cylinder are shown in Table 7. These parameters at 3 and 6 months are also shown stratified by preoperative cycloplegic cylinder in Table 8 and by preoperative cycloplegic refraction spherical equivalent (CRSE) in Table 9.

The effectiveness data meet the criteria established in the FDA Guidance Document for at least 85% of eyes achieving a UCVA of 20/40 or better and accuracy of MRSE within 0.50D in at least 50% of eyes and within 1.00D in 75% of eyes at all postoperative intervals.

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|  Table 7. Summary of Key Effectiveness Parameters Over Time  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Effectiveness Parameters |   | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  UCVA 20/20 or better if Preop BSCVA 20/20 or better | n/N | 68/94 | 60/94 | 67/94 | 64/92  |
|   |  % | 72.3% | 63.8% | 71.3% | 69.6%  |
|   |  CI | (62.2, 81.1) | (53.3, 73.5) | (61.0, 80.1) | (59.1, 78.7)  |
|  UCVA 20/20 or better | n/N | 70/110 | 62/110 | 70/110 | 66/108  |
|   |  % | 63.6% | 56.4% | 63.6% | 61.1%  |
|   |  CI | (53.9, 72.6) | (46.6, 65.8) | (53.9, 72.6) | (51.3, 70.3)  |
|  UCVA 20/25 or better | n/N | 95/110 | 89/110 | 96/110 | 91/108  |
|   |  % | 86.4% | 80.9% | 87.3% | 84.3%  |
|   |  CI | (78.5, 92.2) | (72.3, 87.8) | (79.6, 92.9) | (76.0, 90.6)  |
|  UCVA 20/40 or better | n/N | 106/110 | 105/110 | 108/110 | 101/108  |
|   |  % | 96.4% | 95.5% | 98.2% | 93.5%  |
|   |  CI | (91.0, 99.0) | (89.7, 98.5) | (93.6, 99.8) | (87.1, 97.4)  |
|  MRSE ± 0.50D of intended | n/N | 79/110 | 78/110 | 84/110 | 81/108  |
|   |  % | 71.8% | 70.9% | 76.4% | 75.0%  |
|   |  CI | (62.4, 80.0) | (61.5, 79.2) | (67.3, 83.9) | (65.7, 82.8)  |
|  MRSE ± 1.00D of intended | n/N | 104/110 | 102/110 | 100/110 | 96/108  |
|   |  % | 94.5% | 92.7% | 90.9% | 88.9%  |
|   |  CI | (88.5, 98.0) | (86.2, 96.8) | (83.9, 95.6) | (81.4, 94.1)  |
|  MRSE ± 2.00D of intended | n/N | 109/110 | 109/110 | 110/110 | 108/108  |
|   |  % | 99.1% | 99.1% | 100.0% | 100.0%  |
|   |  CI | (95.0, 100.0) | (95.0, 100.0) | (96.7, 100.0) | (96.6, 100.0)  |
|  Cylinder magnitude ≤ 0.50D of intended | n/N | 71/110 | 73/110 | 71/110 | 66/108  |
|   |  % | 64.5% | 66.4% | 64.5% | 61.1%  |
|   |  CI | (54.9, 73.4) | (56.7, 75.1) | (54.9, 73.4) | (51.3, 70.3)  |
|  Cylinder magnitude ≤ 1.00D of intended | n/N | 96/110 | 100/110 | 98/110 | 95/108  |
|   |  % | 87.3% | 90.9% | 89.1% | 88.0%  |
|   |  CI | (79.6, 92.9) | (83.9, 95.6) | (81.7, 94.2) | (80.3, 93.4)  |
|  Cylinder magnitude ≤ 2.00D of intended | n/N | 108/110 | 109/110 | 109/110 | 107/108  |
|   |  % | 98.2% | 99.1% | 99.1% | 99.1%  |
|   |  CI | (93.6, 99.8) | (95.0, 100.0) | (95.0, 100.0) | (94.9, 100.0)  |

UCVA = Uncorrected Visual Acuity

MRSE = Manifest Refraction Spherical Equivalent

BSCVA = Best Spectacle Corrected Visual Acuity

CI = 95% Confidence Interval D = Diopter

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|  Table 8. Summary of Key Effectiveness Parameters at 3 and 6 Months Stratified by Diopter (D) of Preoperative Cycloplegic Cylinder  |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  3 MONTHS  |   |   |   |   |   |   |   |
|  Effectiveness Parameters |   | -1.00 to -1.99 | -2.00 to -2.99 | -3.00 to -3.99 | -4.00 to -4.99 | -5.00 to -6.00 | Total  |
|  UCVA 20/20 or better if Preop BSCVA 20/20 or better | n/N % | 16/22 72.7% | 20/36 55.6% | 18/23 78.3% | 5/9 55.6% | 1/4 25.0% | 60/94 63.8%  |
|  UCVA 20/20 or better | n/N % | 16/24 66.7% | 21/37 56.8% | 18/25 72.0% | 6/17 35.3% | 1/7 14.3% | 62/110 56.4%  |
|  UCVA 20/25 or better | n/N % | 24/24 100.0% | 28/37 75.7% | 23/25 92.0% | 12/17 70.6% | 2/7 28.6% | 89/110 80.9%  |
|  UCVA 20/40 or better | n/N % | 24/24 100.0% | 33/37 89.2% | 25/25 100.0% | 17/17 100.0% | 6/7 85.7% | 105/110 95.5%  |
|  MRSE ± 0.50D of intended | n/N % | 23/24 95.8% | 25/37 67.6% | 17/25 68.0% | 9/17 52.9% | 4/7 57.1% | 78/110 70.9%  |
|  MRSE ± 1.00D of intended | n/N % | 24/24 100.0% | 35/37 94.6% | 23/25 92.0% | 14/17 82.4% | 6/7 85.7% | 102/110 92.7%  |
|  RSE ± 2.00D of intended | n/N % | 24/24 100.0% | 37/37 100.0% | 25/25 100.0% | 16/17 94.1% | 7/7 100.0% | 109/110 99.1%  |
|  Cylinder magnitude ≤ 0.50D of intended | n/N % | 20/24 83.3% | 25/37 67.6% | 14/25 56.0% | 13/17 76.5% | 1/7 14.3% | 73/110 66.4%  |
|  Cylinder magnitude ≤ 1.00D of intended | n/N % | 24/24 100.0% | 36/37 97.3% | 23/25 92.0% | 14/17 82.4% | 3/7 42.9% | 100/110 90.9%  |
|  Cylinder magnitude ≤ 2.00D of intended | n/N % | 24/24 100.0% | 37/37 100.0% | 25/25 100.0% | 17/17 100.0% | 6/7 85.7% | 109/110 99.1%  |
|  6 MONTHS  |   |   |   |   |   |   |   |
|  Effectiveness Parameters |   | -1.00 to -1.99 | -2.00 to -2.99 | -3.00 to -3.99 | -4.00 to -4.99 | -5.00 to -6.00 | Total  |
|  UCVA 20/20 or better if Preop BSCVA 20/20 or better | n/N % | 21/22 95.5% | 19/36 52.8% | 20/23 87.0% | 7/9 77.8% | 0/4 0.0% | 67/94 71.3%  |
|  UCVA 20/20 or better | n/N % | 21/24 87.5% | 20/37 54.1% | 20/25 80.0% | 9/17 52.9% | 0/7 0.0% | 70/110 63.6%  |
|  UCVA 20/25 or better | n/N % | 24/24 100.0% | 29/37 78.4% | 25/25 100.0% | 14/17 82.4% | 4/7 57.1% | 96/110 87.3%  |
|  UCVA 20/40 or better | n/N % | 24/24 100.0% | 35/37 94.6% | 25/25 100.0% | 17/17 100.0% | 7/7 100.0% | 108/110 98.2%  |
|  MRSE ± 0.50D of intended | n/N % | 24/24 100.0% | 28/37 75.7% | 18/25 72.0% | 10/17 58.8% | 4/7 57.1% | 84/110 76.4%  |
|  MRSE ± 1.00D of intended | n/N % | 24/24 100.0% | 34/37 91.9% | 22/25 88.0% | 14/17 82.4% | 6/7 85.7% | 100/110 90.9%  |
|  MRSE ± 2.00D of intended | n/N % | 24/24 100.0% | 37/37 100.0% | 25/25 100.0% | 17/17 100.0% | 7/7 100.0% | 110/110 100.0%  |
|  Cylinder magnitude ≤ 0.50D of intended | n/N % | 19/24 79.2% | 24/37 64.9% | 15/25 60.0% | 11/17 64.7% | 2/7 28.6% | 71/110 64.5%  |
|  Cylinder magnitude ≤ 1.00D of intended | n/N % | 23/24 95.8% | 35/37 94.6% | 24/25 96.0% | 14/17 82.4% | 2/7 28.6% | 98/110 89.1%  |
|  Cylinder magnitude ≤ 2.00D of intended | n/N % | 24/24 100.0% | 37/37 100.0% | 25/25 100.0% | 17/17 100.0% | 6/7 85.7% | 109/110 99.1%  |

UCVA = Uncorrected Visual Acuity

MRSE = Manifest Refraction Spherical Equivalent

BSCVA = Best Spectacle Corrected Visual Acuity

D Diopter

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|  Table 9. Summary of Key Effectiveness Parameters at 3 and 6 Months Stratified by Diopter (D) of Preoperative Cycloplegic Refraction Spherical Equivalent  |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  3 MONTHS  |   |   |   |   |   |   |
|  Effectiveness Parameters |   | -1.00 to -2.00 | 0.00 to -0.99 | +0.01 to +0.99 | +1.00 to +2.00 | Total  |
|  UCVA 20/20 or better if Preop BSCVA 20/20 or better | n/N | 5/6 | 24/41 | 24/36 | 7/11 | 60/94  |
|   |  % | 83.3% | 58.5% | 66.7% | 63.6% | 63.8%  |
|  UCVA 20/20 or better | n/N | 5/8 | 24/45 | 26/45 | 7/12 | 62/110  |
|   |  % | 62.5% | 53.3% | 57.8% | 58.3% | 56.4%  |
|  UCVA 20/25 or better | n/N | 7/8 | 39/45 | 34/45 | 9/12 | 89/110  |
|   |  % | 87.5% | 86.7% | 75.6% | 75.0% | 80.9%  |
|  UCVA 20/40 or better | n/N | 8/8 | 43/45 | 43/45 | 11/12 | 105/110  |
|   |  % | 100.0% | 95.6% | 95.6% | 91.7% | 95.5%  |
|  MRSE ± 0.50D of intended | n/N | 7/8 | 35/45 | 27/45 | 9/12 | 78/110  |
|   |  % | 87.5% | 77.8% | 60.0% | 75.0% | 70.9%  |
|  MRSE ± 1.00D of intended | n/N | 8/8 | 42/45 | 41/45 | 11/12 | 102/110  |
|   |  % | 100.0% | 93.3% | 91.1% | 91.7% | 92.7%  |
|  MRSE ± 2.00D of intended | n/N | 8/8 | 45/45 | 44/45 | 12/12 | 109/110  |
|   |  % | 100.0% | 100.0% | 97.8% | 100.0% | 99.1%  |
|  Cylinder magnitude ≤ 0.50D of intended | n/N | 4/8 | 30/45 | 32/45 | 7/12 | 73/110  |
|   |  % | 50.0% | 66.7% | 71.1% | 58.3% | 66.4%  |
|  Cylinder magnitude ≤ 1.00D of intended | n/N | 8/8 | 40/45 | 42/45 | 10/12 | 100/110  |
|   |  % | 100.0% | 88.9% | 93.3% | 83.3% | 90.9%  |
|  Cylinder magnitude ≤ 2.00D of intended | n/N | 8/8 | 44/45 | 45/45 | 12/12 | 109/110  |
|   |  % | 100.0% | 97.8% | 100.0% | 100.0% | 99.1%  |
|  6 MONTHS  |   |   |   |   |   |   |
|  Effectiveness Parameters |   | -1.00 to -2.00 | 0.00 to -0.99 | +0.01 to +0.99 | +1.00 to +2.00 | Total  |
|  UCVA 20/20 or better if Preop BSCVA 20/20 or better | n/N | 5/6 | 29/41 | 27/36 | 6/11 | 67/94  |
|   |  % | 83.3% | 70.7% | 75.0% | 54.5% | 71.3%  |
|  UCVA 20/20 or better | n/N | 6/8 | 29/45 | 29/45 | 6/12 | 70/110  |
|   |  % | 75.0% | 64.4% | 64.4% | 50.0% | 63.6%  |
|  UCVA 20/25 or better | n/N | 8/8 | 41/45 | 36/45 | 11/12 | 96/110  |
|   |  % | 100.0% | 91.1% | 80.0% | 91.7% | 87.3%  |
|  UCVA 20/40 or better | n/N | 8/8 | 44/45 | 45/45 | 11/12 | 108/110  |
|   |  % | 100.0% | 97.8% | 100.0% | 91.7% | 98.2%  |
|  MRSE ± 0.50D of intended | n/N | 7/8 | 34/45 | 34/45 | 9/12 | 84/110  |
|   |  % | 87.5% | 75.6% | 75.6% | 75.0% | 76.4%  |
|  MRSE ± 1.00D of intended | n/N | 8/8 | 42/45 | 39/45 | 11/12 | 100/110  |
|   |  % | 100.0% | 93.3% | 86.7% | 91.7% | 90.9%  |
|  MRSE ± 2.00D of intended | n/N | 8/8 | 45/45 | 45/45 | 12/12 | 110/110  |
|   |  % | 100.0% | 100.0% | 100.0% | 100.0% | 100.0%  |
|  Cylinder magnitude ≤ 0.50D of intended | n/N | 4/8 | 27/45 | 33/45 | 7/12 | 71/110  |
|   |  % | 50.0% | 60.0% | 73.3% | 58.3% | 64.5%  |
|  Cylinder magnitude ≤ 1.00D of intended | n/N | 8/8 | 39/45 | 42/45 | 9/12 | 98/110  |
|   |  % | 100.0% | 86.7% | 93.3% | 75.0% | 89.1%  |
|  Cylinder magnitude ≤ 2.00D of intended | n/N | 8/8 | 44/45 | 45/45 | 12/12 | 109/110  |
|   |  % | 100.0% | 97.8% | 100.0% | 100.0% | 99.1%  |

UCVA = Uncorrected Visual Acuity

MRSE = Manifest Refraction Spherical Equivalent

BSCVA - Best Spectacle Corrected Visual Acuity

D - Diopter

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Uncorrected visual acuity is displayed in Table 10. Preoperatively, 35.5% of eyes had a UCVA of 20/40 or better. At 3 months, the UCVA was 20/20 or better in 56.4% of eyes, 20/25 or better in 80.9% and 20/40 or better in 95.5%. At 6 months, the UCVA was 20/20 or better in 63.6% of eyes, 20/25 or better in 87.3% and 20/40 or better in 98.2%. For those eyes with a preoperative BSCVA of 20/20 or better, a UCVA of 20/20 or better was achieved in 63.8% and 71.3% of eyes at 3 and 6 months, respectively.

|  Table 10. Cumulative Uncorrected Visual Acuity at Distance  |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |  | PREOP | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  20/10 | n/N | 0/110 | 1/110 | 2/110 | 3/110 | 3/108  |
|   |  % | 0.0% | 0.9% | 1.8% | 2.7% | 2.8%  |
|  20/12.5 or better | n/N | 0/110 | 8/110 | 11/110 | 11/110 | 9/108  |
|   |  % | 0.0% | 7.3% | 10.0% | 10.0% | 8.3%  |
|  20/16 or better | n/N | 0/110 | 33/110 | 33/110 | 39/110 | 40/108  |
|   |  % | 0.0% | 30.0% | 30.0% | 35.5% | 37.0%  |
|  20/20 or better | n/N | 1/110 | 70/110 | 62/110 | 70/110 | 66/108  |
|   |  % | 0.9% | 63.6% | 56.4% | 63.6% | 61.1%  |
|  20/25 or better | n/N | 4/110 | 95/110 | 89/110 | 96/110 | 91/108  |
|   |  % | 3.6% | 86.4% | 80.9% | 87.3% | 84.3%  |
|  20/32 or better | n/N | 17/110 | 104/110 | 98/110 | 104/110 | 99/108  |
|   |  % | 15.5% | 94.5% | 89.1% | 94.5% | 91.7%  |
|  20/40 or better | n/N | 39/110 | 106/110 | 105/110 | 108/110 | 101/108  |
|   |  % | 35.5% | 96.4% | 95.5% | 98.2% | 93.5%  |
|  20/50 or better | n/N | 53/110 | 109/110 | 110/110 | 109/110 | 107/108  |
|   |  % | 48.2% | 99.1% | 100.0% | 99.1% | 99.1%  |
|  20/63 or better | n/N | 68/110 | 110/110 | 110/110 | 110/110 | 107/108  |
|   |  % | 61.8% | 100.0% | 100.0% | 100.0% | 99.1%  |
|  20/80 or better | n/N | 84/110 | 110/110 | 110/110 | 110/110 | 108/108  |
|   |  % | 76.4% | 100.0% | 100.0% | 100.0% | 100.0%  |
|  20/100 or better | n/N | 98/110 | 110/110 | 110/110 | 110/110 | 108/108  |
|   |  % | 89.1% | 100.0% | 100.0% | 100.0% | 100.0%  |
|  Worse than 20/100 | n/N | 12/110 | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 10.9% | 0.0% | 0.0% | 0.0% | 0.0%  |

A comparison of postoperative UCVA to preoperative BSCVA after CustomCornea® LASIK surgery is presented in Table 11 with differences based on lines of visual acuity. A postoperative UCVA equal to or better than the preoperative BSCVA was achieved in 56.4% and 60.0% of eyes at 3 and 6 months, respectively.

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|  Table 11. Postoperative Uncorrected Visual Acuity Compared to Preoperative Best Spectacle Corrected Visual Acuity  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |  | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  UCVA 2 Lines Better | n/N | 0/110 | 0/110 | 2/110 | 2/108  |
|  Than Preop BSCVA | % | 0.0% | 0.0% | 1.8% | 1.9%  |
|  UCVA 1 Line Better | n/N | 13/110 | 18/110 | 19/110 | 20/108  |
|  Than Preop BSCVA | % | 11.8% | 16.4% | 17.3% | 18.5%  |
|  UCVA Equal* to | n/N | 53/110 | 44/110 | 45/110 | 43/108  |
|  Preop BSCVA | % | 48.2% | 40.0% | 40.9% | 39.8%  |
|  UCVA 1 Line Worse | n/N | 26/110 | 21/110 | 29/110 | 21/108  |
|  Than Preop BSCVA | % | 23.6% | 19.1% | 26.4% | 19.4%  |
|  UCVA 2 Lines Worse | n/N | 9/110 | 13/110 | 7/110 | 11/108  |
|  Than Preop BSCVA | % | 8.2% | 11.8% | 6.4% | 10.2%  |
|  UCVA >2 Lines Worse | n/N | 9/110 | 14/110 | 8/110 | 11/108  |
|  Than Preop BSCVA | % | 8.2% | 12.7% | 7.3% | 10.2%  |

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual Acuity

* Equal visual acuity is within 2 or 3 letters on the same line of a visual acuity chart

As shown in Table 12, accuracy of MRSE was within 0.50D of emmetropia in 70.9% of eyes, within 1.00D in 92.7% and within 2.00D in 99.1% at 3 months. At 6 months, the MRSE was within 0.50D of emmetropia in 76.4% of eyes, within 1.00D in 90.9% and within 2.00D in 100%. Of the eyes that did not achieve an MRSE within 1.00D of emmetropia, 5.5% at 3 months and 7.3% at 6 months had more than +1.00D of hyperopia, whereas 1.8% at 3 and 6 months had more than -1.00D of myopia. One eye (0.9%) had more than +2.00D of hyperopia by MRSE at 3 months.

|  Table 12. Accuracy of Manifest Refraction Spherical Equivalent  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |  | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  ± 0.50D | n/N | 79/110 | 78/110 | 84/110 | 81/108  |
|   |  % | 71.8% | 70.9% | 76.4% | 75.0%  |
|  ± 1.00D | n/N | 104/110 | 102/110 | 100/110 | 96/108  |
|   |  % | 94.5% | 92.7% | 90.9% | 88.9%  |
|  ± 2.00D | n/N | 109/110 | 109/110 | 110/110 | 108/108  |
|   |  % | 99.1% | 99.1% | 100.0% | 100.0%  |
|  > ± 2.00D | n/N | 1/110 | 1/110 | 0/110 | 0/108  |
|   |  % | 0.9% | 0.9% | 0.0% | 0.0%  |
|  Postop Hyperopic MRSE > +1.00D | n/N | 5/110 | 6/110 | 8/110 | 9/108  |
|   |  % | 4.5% | 5.5% | 7.3% | 8.3%  |
|  Postop Hyperopic MRSE > +2.00D | n/N | 1/110 | 1/110 | 0/110 | 0/108  |
|   |  % | 0.9% | 0.9% | 0.0% | 0.0%  |
|  Postop Myopic MRSE < -1.00D | n/N | 1/110 | 2/110 | 2/110 | 3/108  |
|   |  % | 0.9% | 1.8% | 1.8% | 2.8%  |
|  Postop Myopic MRSE < -2.00D | n/N | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0%  |

MRSE = Manifest Refraction Spherical Equivalent

D = Diopter

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Accuracy of manifest refraction is displayed for the preoperative hyperopic meridian in Table 13 and preoperative myopic meridian in Table 14. Slight undercorrection along the preoperative hyperopic meridian was observed based on a mean correction error of +0.15D ± 0.69D at 3 months and +0.20D ± 0.63D at 6 months. Along the preoperative myopic meridian, slight undercorrection was observed based on a mean correction error of -0.09D ± 0.67D at 3 months and -0.07D ± 0.61D at 6 months.

|  Table 13. Accuracy of Manifest Refraction in Preoperative Hyperopic Meridian  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Correction Error |   | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  Mean ± SD (D) |   | +0.07 ± 0.68 | +0.15 ± 0.69 | +0.20 ± 0.63 | +0.17 ± 0.63  |
|  0.00 ± 0.50D | n/N | 79/110 | 74/110 | 77/110 | 73/108  |
|   |  % | 71.8% | 67.3% | 70.0% | 67.6%  |
|  Undercorrected (Postoperative Hyperopia)  |   |   |   |   |   |
|  > 0.50 to 1.00D | n/N | 10/110 | 18/110 | 16/110 | 15/108  |
|   |  % | 9.1% | 16.4% | 14.5% | 13.9%  |
|  > 1.00 to 2.00D | n/N | 4/110 | 7/110 | 8/110 | 7/108  |
|   |  % | 3.6% | 6.4% | 7.3% | 6.5%  |
|  > 2.00D | n/N | 2/110 | 2/110 | 2/110 | 2/108  |
|   |  % | 1.8% | 1.8% | 1.8% | 1.9%  |
|  Overcorrected (Postoperative Myopia)  |   |   |   |   |   |
|  > 0.50 to 1.00D | n/N | 10/110 | 5/110 | 5/110 | 10/108  |
|   |  % | 9.1% | 4.5% | 4.5% | 9.3%  |
|  > 1.00 to 2.00D | n/N | 5/110 | 4/110 | 2/110 | 1/108  |
|   |  % | 4.5% | 3.6% | 1.8% | 0.9%  |
|  > 2.00D | n/N | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0%  |

|  Table 14. Accuracy of Manifest Refraction in Preoperative Myopic Meridian  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Correction Error |   | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  Mean ± SD (D) |   | -0.12 ± 0.64 | -0.09 ± 0.67 | -0.07 ± 0.61 | -0.13 ± 0.66  |
|  0.00 ± 0.50D | n/N | 73/110 | 67/110 | 71/110 | 66/108  |
|   |  % | 66.4% | 60.9% | 64.5% | 61.1%  |
|  Undercorrected (Postoperative Myopia)  |   |   |   |   |   |
|  > 0.50 to 1.00D | n/N | 17/110 | 20/110 | 17/110 | 19/108  |
|   |  % | 15.5% | 18.2% | 15.5% | 17.6%  |
|  > 1.00 to 2.00D | n/N | 6/110 | 5/110 | 5/110 | 6/108  |
|   |  % | 5.5% | 4.5% | 4.5% | 5.6%  |
|  > 2.00D | n/N | 1/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.9% | 0.0% | 0.0% | 0.0%  |
|  Overcorrected (Postoperative Hyperopia)  |   |   |   |   |   |
|  > 0.50 to 1.00D | n/N | 9/110 | 11/110 | 8/110 | 10/108  |
|   |  % | 8.2% | 10.0% | 7.3% | 9.3%  |
|  > 1.00 to 2.00D | n/N | 4/110 | 7/110 | 9/110 | 7/108  |
|   |  % | 3.6% | 6.4% | 8.2% | 6.5%  |
|  > 2.00D | n/N | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0%  |

SD = Standard Deviation

D - Diopter

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Table 15 displays the accuracy of manifest sphere and cylinder magnitude. Postoperative manifest sphere was within 0.50D of emmetropia in 71.3% of eyes, within 1.00D in 87.0% and within 2.00D in 98.1% at 3 months. Manifest sphere was within 0.50D of emmetropia in 70.4% of eyes, within 1.00D in 88.0% and within 2.00D in 98.1% at 6 months.

Postoperative manifest cylinder magnitude was ≤ 0.50D of emmetropia in 66.4% of eyes, ≤ 1.00D in 90.9% and ≤ 2.00D in 99.1% at 3 months. Cylinder magnitude was ≤ 0.50D in 64.5% of eyes, ≤ 1.00D in 89.1% and ≤ 2.00D in 99.1% at 6 months.

|  Table 15. Accuracy of Manifest Sphere and Cylinder Magnitude  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Sphere* |   | 1 MONTH (N=108) | 3 MONTHS (N=108) | 6 MONTHS (N=108) | 9 MONTHS (N=106)  |
|  Postop Mean ± SD (D) |   | +0.27 ± 0.65 | +0.31 ± 0.68 | +0.35 ± 0.62 | +0.33 ± 0.64  |
|  Attempted Mean ± SD (D) |   | +1.20 ± 0.88 | +1.20 ± 0.88 | +1.20 ± 0.88 | +1.19 ± 0.89  |
|  Achieved Mean ± SD (D) |   | +0.92 ± 0.98 | +0.89 ± 1.03 | +0.85 ± 1.00 | +0.87 ± 1.04  |
|  % Achieved |   | 69 ± 85 | 64 ± 79 | 61 ± 85 | 60 ± 91  |
|  ± 0.50D | n/N | 81/108 | 77/108 | 76/108 | 77/106  |
|   |  % | 75.0% | 71.3% | 70.4% | 72.6%  |
|  ± 1.00D | n/N | 99/108 | 94/108 | 95/108 | 94/106  |
|   |  % | 91.7% | 87.0% | 88.0% | 88.7%  |
|  ± 2.00D | n/N | 106/108 | 106/108 | 106/108 | 104/106  |
|   |  % | 98.1% | 98.1% | 98.1% | 98.1%  |
|  Cylinder |   | 1 MONTH (N=110) | 3 MONTHS (N=110) | 6 MONTHS (N=110) | 9 MONTHS (N=108)  |
|  Postop Mean ± SD (D) |   | -0.58 ± 0.55 | -0.53 ± 0.53 | -0.55 ± 0.47 | -0.59 ± 0.46  |
|  Attempted Mean ± SD (D) |   | -2.89 ± 1.21 | -2.89 ± 1.21 | -2.89 ± 1.21 | -2.90 ± 1.21  |
|  Achieved Mean ± SD (D) |   | -2.30 ± 1.12 | -2.36 ± 1.12 | -2.34 ± 1.15 | -2.31 ± 1.17  |
|  % Achieved |   | 78 ± 20 | 81 ± 18 | 79 ± 18 | 77 ± 20  |
|  ≤ 0.50D | n/N | 71/110 | 73/110 | 71/110 | 66/108  |
|   |  % | 64.5% | 66.4% | 64.5% | 61.1%  |
|  ≤ 1.00D | n/N | 96/110 | 100/110 | 98/110 | 95/108  |
|   |  % | 87.3% | 90.9% | 89.1% | 88.0%  |
|  ≤ 2.00D | n/N | 108/110 | 109/110 | 109/110 | 107/108  |
|   |  % | 98.2% | 99.1% | 99.1% | 99.1%  |

* Excludes two eyes with a preoperative manifest sphere of 0D.

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Effectiveness of astigmatism correction at 3 and 6 months was evaluated based on the percentage reduction in cylinder magnitude and by vector analysis (Table 16). The mean percentage reduction in absolute manifest cylinder was 80.6% at 3 months and 79.1% at 6 months with an overall trend for a greater percentage reduction in eyes with higher preoperative cylinder. The mean correction ratio based on vector analysis of manifest cylinder was 0.92 at 3 months and 0.91 at 6 months.

|  Table 16. Effectiveness of Astigmatic Correction By Manifest Cylinder  |   |   |   |
| --- | --- | --- | --- |
|  3 MONTHS  |   |   |   |
|  Preoperative Cylinder | N | Mean Percentage Reduction in Cylinder Magnitude | Vector Analysis Mean ± SD Correction Ratio  |
|  All | 110 | 80.6% | 0.92 ± 0.18  |
|  1.00 to < 2.00D | 26 | 75.9% | 0.86 ± 0.21  |
|  2.00 to < 3.00D | 34 | 79.9% | 0.94 ± 0.17  |
|  3.00 to < 4.00D | 26 | 84.1% | 0.93 ± 0.14  |
|  4.00 to < 5.00D | 16 | 87.1% | 1.01 ± 0.12  |
|  5.00 to 6.00D | 8 | 74.4% | 0.83 ± 0.24  |
|  6 MONTHS  |   |   |   |
|  Preoperative Cylinder | N | Mean Percentage Reduction in Cylinder Magnitude | Vector Analysis Mean ± SD Correction Ratio  |
|  All | 110 | 79.1% | 0.91 ± 0.17  |
|  1.00 to < 2.00D | 26 | 72.3% | 0.84 ± 0.20  |
|  2.00 to < 3.00D | 34 | 77.3% | 0.92 ± 0.17  |
|  3.00 to < 4.00D | 26 | 83.9% | 0.93 ± 0.16  |
|  4.00 to < 5.00D | 16 | 87.0% | 0.98 ± 0.12  |
|  5.00 to 6.00D | 8 | 78.0% | 0.86 ± 0.20  |

SD = Standard Deviation

D = Diopter

Correction Ratio is the ratio of achieved vs. intended vector magnitude

Table 17 presents the manifest and cycloplegic phoropter refraction over time and the wavefront refraction from the wavefront measurement under cycloplegic conditions.

The mean manifest spherical equivalent was +0.03D ± 0.62D at 3 months and +0.06D ± 0.57D at 6 months. The mean cycloplegic and wavefront spherical equivalents were similar over time. As expected under cycloplegic conditions, the cycloplegic and wavefront spherical equivalents reflected more hyperopia that was within 0.50D of the manifest spherical equivalent preoperatively and postoperatively.

The mean manifest cylinder was -0.53D ± 0.53D at 3 months and -0.55D ± 0.47D at 6 months. The mean cycloplegic cylinder was similar to the manifest cylinder over time. The mean wavefront cylinder was within 0.25D of the manifest and cycloplegic refractions postoperatively.

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|  Table 17. Mean Refraction Over Time  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Mean ± Standard Deviation | PREOP | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  Manifest Refraction (D) | N=110 | N=110 | N=110 | N=110 | N=108  |
|  Spherical Equivalent | -0.27 ± 0.67 | -0.03 ± 0.59 | 0.03 ± 0.62 | 0.06 ± 0.57 | 0.02 ± 0.59  |
|  Cylinder | -2.89 ± 1.21 | -0.58 ± 0.55 | -0.53 ± 0.53 | -0.55 ± 0.47 | -0.59 ± 0.46  |
|  Cycloplegic Refraction (D)* | N=110 | -- | N=110 | N=108 | --  |
|  Spherical Equivalent | 0.06 ± 0.65 | -- | 0.49 ± 0.56 | 0.44 ± 0.56 | --  |
|  Cylinder | -2.90 ± 1.20 | -- | -0.49 ± 0.51 | -0.52 ± 0.49 | --  |
|  Wavefront Refraction (D)** | N=110 | N=103 | N=100 | N=103 | N=100  |
|  Spherical Equivalent | 0.04 ± 0.71 | 0.35 ± 0.45 | 0.44 ± 0.46 | 0.31 ± 0.46 | 0.39 ± 0.52  |
|  Cylinder | -2.91 ± 1.25 | -0.71 ± 0.49 | -0.69 ± 0.47 | -0.65 ± 0.35 | -0.74 ± 0.52  |

Refractions at the spectacle plane

D = Diopter

* Cycloplegic refraction not required at 1 month and 9 months

**Wavefront measurement under cycloplegic conditions with refraction analyzed over 3.5mm diameter

# d. Wavefront Outcomes

Table 18 displays the mean change from preoperative in total root mean square (RMS) wavefront error and in higher-order aberrations through 6th-order. The mean change in total RMS wavefront error decreased by 64.1% at 3 months and 67.2% at 6 months from preoperative. Higher-order aberrations were not significantly changed from preoperative on average with an increase of 2.3% at 3 months and 2.2% at 6 months. Spherical aberration decreased in magnitude at 3 and 6 months from preoperative with a mean directional shift from positive spherical aberration preoperatively (0.233μm) towards slightly negative spherical aberration at 3 months (-0.003μm) and 6 months (-0.007μm).

|  Table 18. Mean Change in Aberrations Up to 6th-Order From Preoperative*  |   |   |   |   |
| --- | --- | --- | --- | --- |
|   | 3 MONTHS (N=100) |   | 6 MONTHS (N=103)  |   |
|  Aberration | Mean Change (μm) | Mean Change (%) | Mean Change (μm) | Mean Change (%)  |
|  Total RMS Error | -1.905 | -64.1 | -1.998 | -67.2  |
|  Higher-Order | 0.010 | 2.3 | 0.010 | 2.2  |
|  Coma | 0.030 | 12.5 | 0.034 | 13.9  |
|  Trefoil | 0.008 | 4.0 | 0.005 | 2.7  |
|  Spherical Aberration Magnitude † | -0.114 | -48.4 | -0.101 | -42.8  |
|  Spherical Aberration Value ‡ | -0.236 | -101.2 | -0.240 | -102.9  |
|  Secondary Astigmatism | 0.073 | 92.8 | 0.066 | 84.3  |
|  Tetrafoil | 0.023 | 30.4 | 0.027 | 35.3  |
|  Combined 5th and 6th Order | 0.037 | 49.5 | 0.035 | 46.6  |

RMS = Root Mean Square

Wavefront Analysis Diameter = 6.0mm

* Positive change represents increase from preop; Negative change represents decrease from preop
† Based on absolute spherical aberration magnitude ‡ Based on signed spherical aberration value

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Summary of Safety and Effectiveness

At 3 and 6 months, 100% of eyes had a reduction in total RMS error from preoperative. A reduction in higher-order aberrations from preoperative was observed in 55.0% of eyes at 3 months and 54.4% at 6 months (Table 19).

|  **Table 19. Percentage of Eyes with Reduced Aberrations Up to 6^{th}-Order From Preoperative**  |   |   |
| --- | --- | --- |
|   | **3 MONTHS (N=100)** | **6 MONTHS (N=103)**  |
|  **Aberration** | **% Eyes with Reduction in Aberrations**  |   |
|  Total RMS Error | 100.0% | 100.0%  |
|  Higher-Order | 55.0% | 54.4%  |
|  Coma | 48.0% | 49.5%  |
|  Trefoil | 49.0% | 45.6%  |
|  Spherical Aberration Magnitude † | 80.0% | 78.6%  |
|  Secondary Astigmatism | 18.0% | 17.5%  |
|  Tetrafoil | 32.0% | 32.0%  |
|  Combined 5^{th} and 6^{th} Order | 18.0% | 17.5%  |

RMS = Root Mean Square Wavefront Analysis Diameter = 6.0mm

† Reduction in absolute spherical aberration magnitude

Wavefront-guided CustomCornea® LASIK was compared to the baseline established for Conventional LASIK correction of mixed astigmatism using phoropter refraction for eyes treated under the same study protocol over the same preoperative cycloplegic refractive range of -1.00D to -3.50D cylinder. Wavefront aberrations at 3 and 6 months were analyzed up to 4th-order for the Comparison Cohort (Table 20).

Compared to Conventional eyes, CustomCornea® eyes showed:

- statistically significantly lower mean amplitudes of total RMS error, higher-order aberrations, trefoil, spherical aberration magnitude, secondary astigmatism and tetrafoil at 3 and 6 months postoperatively (t-test with unequal variance; \( p < 0.05 \)).
- greater mean decrease in total RMS error from preoperative at 3 and 6 months.
- a mean decrease in higher-order aberrations from preoperative compared to a mean increase for Conventional eyes at 3 and 6 months.

Spherical aberration value for the CustomCornea® eyes was positive preoperatively (0.235μm) and at 3 months (0.041μm) and 6 months (0.029μm). Similarly for the Conventional eyes, spherical aberration value was positive preoperatively (0.176μm) and at 3 months (0.099μm) and 6 months (0.112μm).

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|  Table 20. Mean Change in Aberrations Up to 4^{th}-Order from Preoperative*: CustomCornea^{®} vs. Conventional Comparison Cohort  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  3 MONTHS  |   |   |   |   |   |
|  Aberration | CustomCornea^{®} (N=74) |   | Conventional (N=26) |   | p-Value §  |
|   |  μm | % | μm | %  |   |
|  Total RMS Error | -1.509 | -62.2 | -0.990 | -39.8 | <0.0001  |
|  Higher-Order | -0.060 | -13.7 | 0.199 | 51.3 | <0.0001  |
|  Coma | -0.008 | -3.3 | 0.108 | 55.7 | 0.1542  |
|  Trefoil | -0.021 | -11.1 | 0.167 | 91.6 | <0.0001  |
|  Spherical Aberration Magnitude † | -0.132 | -56.0 | -0.016 | -8.9 | 0.0167  |
|  Spherical Aberration Value ‡ | -0.195 | -82.8 | -0.076 | -43.4 | 0.1332  |
|  Secondary Astigmatism | 0.046 | 62.3 | 0.086 | 98.8 | 0.0142  |
|  Tetrafoil | 0.021 | 30.3 | 0.048 | 51.9 | 0.0029  |
|  6 MONTHS  |   |   |   |   |   |
|  Aberration | CustomCornea^{®} (N=81) |   | Conventional (N=25) |   | p-Value §  |
|   |  μm | % | μm | %  |   |
|  Total RMS Error | -1.534 | -63.2 | -0.985 | -39.6 | <0.0001  |
|  Higher-Order | -0.053 | -12.0 | 0.232 | 59.8 | <0.0001  |
|  Coma | -0.010 | -3.9 | 0.135 | 69.5 | 0.0905  |
|  Trefoil | -0.014 | -7.7 | 0.160 | 88.1 | 0.0001  |
|  Spherical Aberration Magnitude † | -0.120 | -51.1 | -0.008 | -4.6 | 0.0224  |
|  Spherical Aberration Value ‡ | -0.206 | -87.5 | -0.064 | -36.4 | 0.0421  |
|  Secondary Astigmatism | 0.047 | 63.4 | 0.091 | 104.3 | 0.0272  |
|  Tetrafoil | 0.027 | 38.3 | 0.066 | 72.3 | 0.0004  |

RMS = Root Mean Square

Wavefront Analysis Diameter = 6.0mm

* Positive change represents increase from preop; Negative change represents decrease from preop

† Based on absolute spherical aberration magnitude ‡ Based on signed spherical aberration value

§ t-test with unequal variance for postoperative comparison between treatment types;

p < 0.05 statistically significant, shown in bold

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As shown in Table 21, more eyes had a reduction in higher-order aberrations after CustomCornea® LASIK compared to after Conventional LASIK at 3 months (66.2% vs. 7.7%) and 6 months (61.7% vs. 8.0%).

|  Table 21. Percentage of Eyes with Reduced Aberrations Up to 4^{th}-Order from Preoperative: CustomCornea® vs. Conventional Comparison Cohort  |   |   |   |   |
| --- | --- | --- | --- | --- |
|   | 3 MONTHS |   | 6 MONTHS  |   |
|  Aberration | CustomCornea® (N=74) | Conventional (N=26) | CustomCornea® (N=81) | Conventional (N=25)  |
|  Total RMS Error | 100.0% | 92.3% | 100.0% | 96.0%  |
|  Higher-Order | 66.2% | 7.7% | 61.7% | 8.0%  |
|  Coma | 55.4% | 19.2% | 55.6% | 28.0%  |
|  Trefoil | 55.4% | 7.7% | 51.9% | 20.0%  |
|  Spherical Aberration Magnitude † | 86.5% | 57.7% | 85.2% | 52.0%  |
|  Secondary Astigmatism | 21.6% | 19.2% | 19.8% | 16.0%  |
|  Tetrafoil | 32.4% | 23.1% | 30.9% | 20.0%  |

RMS = Root Mean Square Wavefront Analysis Diameter = 6.0mm

† Reduction in absolute spherical aberration magnitude

# e. Safety Outcomes

The key safety outcomes by visit are presented in Table 22. These parameters at 3 and 6 months are also shown stratified by preoperative cycloplegic cylinder in Table 23 and by preoperative CRSE in Table 24.

No eyes had a loss of more than 2 lines of BSCVA and one eye (0.9%) had a loss of 2 lines at 1 month. All eyes had a BSCVA within 1 line of preoperative BSCVA at 3 months or later. Preoperative BSCVA was 20/25 or better for all eyes. Postoperative BSCVA was 20/32 or better at all postoperative intervals and 20/25 or better at 3 months or later.

The safety data meet the criteria established in the FDA Guidance Document of less than 5% of eyes with a loss of more than 2 lines of BSCVA, less than 1% having a BSCVA of worse than 20/40, and less than 5% having an increase in cylinder magnitude of more than 2D at all postoperative intervals.

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|  Table 22. Summary of Key Safety Parameters Over Time  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Safety Parameters |   | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  Loss of > 2 Lines BSCVA | n/N | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0%  |
|   |  CI | (0.0, 3.3) | (0.0, 3.3) | (0.0, 3.3) | (0.0, 3.4)  |
|  Loss of 2 Lines BSCVA | n/N | 1/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.9% | 0.0% | 0.0% | 0.0%  |
|   |  CI | (0.0, 5.0) | (0.0, 3.3) | (0.0, 3.3) | (0.0, 3.4)  |
|  BSCVA worse than 20/40 | n/N | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0%  |
|   |  CI | (0.0, 3.3) | (0.0, 3.3) | (0.0, 3.3) | (0.0, 3.4)  |
|  Increase > 2D cylinder magnitude | n/N | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0%  |
|   |  CI | (0.0, 3.3) | (0.0, 3.3) | (0.0, 3.3) | (0.0, 3.4)  |
|  BSCVA worse than 20/25 if 20/20 or better preoperatively | n/N | 1/94 | 0/94 | 0/94 | 0/92  |
|   |  % | 1.1% | 0.0% | 0.0% | 0.0%  |
|   |  CI | (0.0, 5.8) | (0.0, 3.8) | (0.0, 3.8) | (0.0, 3.9)  |

BSCVA = Best Spectacle Corrected Visual Acuity CI = 95% Confidence Interval D = Diopter

|  Table 23. Summary of Key Safety Parameters at 3 and 6 Months Stratified by Diopter (D) of Preoperative Cycloplegic Cylinder  |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  3 MONTHS  |   |   |   |   |   |   |   |
|  Safety Parameters |   | -1.00 to -1.99 | -2.00 to -2.99 | -3.00 to -3.99 | -4.00 to -4.99 | -5.00 to -6.00 | Total  |
|  Loss of > 2 Lines BSCVA | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  Loss of 2 Lines BSCVA | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  BSCVA worse than 20/40 | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  Increase > 2D cylinder magnitude | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  BSCVA worse than 20/25 if 20/20 or better preoperative | n/N | 0/22 | 0/36 | 0/23 | 0/9 | 0/4 | 0/94  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  6 MONTHS  |   |   |   |   |   |   |   |
|  Safety Parameters |   | -1.00 to -1.99 | -2.00 to -2.99 | -3.00 to -3.99 | -4.00 to -4.99 | -5.00 to -6.00 | Total  |
|  Loss of > 2 Lines BSCVA | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  Loss of 2 Lines BSCVA | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  BSCVA worse than 20/40 | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  Increase > 2D cylinder magnitude | n/N | 0/24 | 0/37 | 0/25 | 0/17 | 0/7 | 0/110  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |
|  BSCVA worse than 20/25 if 20/20 or better preoperative | n/N | 0/22 | 0/36 | 0/23 | 0/9 | 0/4 | 0/94  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0% | 0.0% | 0.0%  |

BSCVA = Best Spectacle Corrected Visual Acuity

D = Diopter

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|  Table 24. Summary of Key Safety Parameters at 3 and 6 Months Stratified by Diopter (D) of Preoperative Cycloplegic Refraction Spherical Equivalent  |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  3 MONTHS  |   |   |   |   |   |   |
|  Safety Parameters |   | -1.00 to -2.00 | 0.00 to -0.99 | +0.01 to +0.99 | +1.00 to +2.00 | Total  |
|  Loss of > 2 Lines BSCVA | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  Loss of 2 Lines BSCVA | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  BSCVA worse than 20/40 | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  Increase > 2D cylinder magnitude | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  BSCVA worse than 20/25 if 20/20 or better preoperative | n/N % | 0/6 0.0% | 0/41 0.0% | 0/36 0.0% | 0/11 0.0% | 0/94 0.0%  |
|  6 MONTHS  |   |   |   |   |   |   |
|  Safety Parameters |   | -1.00 to -2.00 | 0.00 to -0.99 | +0.01 to +0.99 | +1.00 to +2.00 | Total  |
|  Loss of > 2 Lines BSCVA | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  Loss of 2 Lines BSCVA | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  BSCVA worse than 20/40 | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  Increase > 2D cylinder magnitude | n/N % | 0/8 0.0% | 0/45 0.0% | 0/45 0.0% | 0/12 0.0% | 0/110 0.0%  |
|  BSCVA worse than 20/25 if 20/20 or better preoperative | n/N % | 0/6 0.0% | 0/41 0.0% | 0/36 0.0% | 0/11 0.0% | 0/94 0.0%  |

BSCVA = Best Spectacle Corrected Visual Acuity

D = Diopter

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Using a standard (high-contrast) visual acuity chart, BSCVA was measured under dim room illumination (10-12 cd/m²). At least 90.9% of eyes had a gain or no change in BSCVA from preoperative at all postoperative intervals (Table 25). A trend for postoperative BSCVA gain of 1 line was observed compared to a loss of 1 line at 3 months (39.1% vs. 6.4%) and at 6 months (38.2% vs. 3.6%). While a small percentage of eyes had a BSCVA gain of 2 lines at 3 months (0.9%) and at 6 months (3.6%), no eyes had a BSCVA loss of 2 lines at 3 months or later.

|  Table 25. Change in Best Spectacle Corrected Visual Acuity  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   | 1 MONTH | 3 MONTHS | 6 MONTHS | 9 MONTHS  |
|  Decrease > 2 Lines | n/N | 0/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.0% | 0.0% | 0.0% | 0.0%  |
|  Decrease 2 Lines | n/N | 1/110 | 0/110 | 0/110 | 0/108  |
|   |  % | 0.9% | 0.0% | 0.0% | 0.0%…

---

**Source:** [https://fda-staging.innolitics.com/device/P970043S022](https://fda-staging.innolitics.com/device/P970043S022)

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