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ALLEGRETTO WAVE® EYE-Q Scanning Spot LASIK Laser System

ADDENDUM Procedure Manual

Photorefractive Keratectomy (PRK) Treatments Information for professional use

WaveLight GmbH Am Wolfsmantel 5

91058 Erlangen, Germany

of 52 ALLEGRETTO WAVE EYE-Q 1010-3 Add. Procedure Manual PRK us / Rev.1a / 16-10-24 Item No.: 6649 2025

This documentation is copyrighted with all rights reserved. Under copyright laws this documentation may not be reproduced or transmitted in whole or in part in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from WaveLight GmbH. Permitted copies must carry the same proprietary and copyright notices as were affixed to the original. Under the law, copying includes also translation into other languages.

Please note that while every effort has been made to ensure that the data given in this documentation is accurate, the information, figures, illustration, tables, specifications and schematics contained herein are subject to change without notice.

All images are representative. The numbers shown in the images are just examples and may not represent typical values. Some sections of this documentation may not apply for all devices. Such sections will be marked accordingly. Other documentations may apply as well for use of the device described herein.

WaveLight® is a registered trademark of WaveLight GmbH. WaveLight® FS200 and WaveLight® EX500 are registered trademarks of WaveLight GmbH. WaveLight® Refractive Suite is a registered trademark of WaveLight GmbH. ALLEGRETTO WAVE® EYE-Q is a registered trademark of WaveLight GmbH. WaveNet™ is a registered trademark of WaveLight GmbH. WaveNet™ Planning Software is a registered trademark of WaveLight GmbH. WaveNet™ Server is a registered trademark of WaveLight GmbH. WaveLight® Analyzer II is a registered trademark of WaveLight GmbH. WaveLight® Oculyzer II is a registered trademark of WaveLight GmbH. WaveLight® OB820 is a registered trademark of WaveLight GmbH. Wavefront Optimized™ is a registered trademark of WaveLight GmbH. Custom Q® is a registered trademark of WaveLight GmbH. PerfectPulse Technology® is a registered trademark of WaveLight GmbH. Right.From the Start.® is a registered trademark of WaveLight GmbH. Accutane® is a registered trademark of Hoffmann-La Roche Inc. Cordarone® is a registered trademark of Wyeth Inc. Imitrex® is a registered trademark of GlaxoSmithKline Inc. Zeiss and OPMI are registered trademarks of Carl Zeiss. Microsoft, Windows™ is a registered trademark of Microsoft Corporation. © Copyright by WaveLight GmbH, Germany All Rights reserved

Using The Ad Procedure Manual PRK

ALLEGRETTO WAVE EYE-Q 1010-3 Add. Procedure Manual PRK us / Rev.1a / 16-10-24 Item No.: 6649 2025 of 52

USING THE AD PROCEDURE MANUAL PRK (Photorefractive Keratectomy Treatments) This manual provides information for the intended clinical use of the ALLEGRETTO WAVE® EYE-Q laser system for Photorefractive Keratectomy (PRK) treatments.

This manual provides only information that is specific for PRK. Refer to the Operator’s Manual of the laser console, to its addendums, its Procedure Manuals and to the User Manuals of the approved accessories for information regarding these components.

Carefully read and understand this manual and all related documents and instructions before using the ALLEGRETTO WAVE® EYE-Q laser system for performing PRK treatments.

Observe all warnings, precautions and contra-indications as described in these documents.

Do not perform adjustments and procedures other than those described in these documents. Failure to do so may result in harm to patient and / or user.

Consult the Table of Contents, Appendices or Indices for specific information. If you have questions that are not addressed in this manual, contact the hotline shown in the Operator’s Manual of the laser console. This Addendum Procedure Manual ALLEGRETTO WAVE® EYE-Q Version 1010-3 is valid as from Notebook Portal Software Version 2.020 (please refer to the Addendum Operator’s Manual Notebook Portal Software).

Typographical Conventions


CAUTION

“Precautions” alert the reader to exercise special care necessary for the safe and effective use of the device.

WARNING

A “Warning” alerts the user to potential serious outcomes to the patient or user in case of non-observance of this warning.

TYPOGRAPHICAL CONVENTIONS The following conventions are used in this manual for Warnings, Precautions and Notes:

NOTE

“Notes” provide helpful or supplementary information to the user.

Notice To Users


CAUTION

RESTRICTED DEVICE

U.S. Federal Law restricts this device to sale, distribution, and use by or on the order of a physician or other licensed practitioner. U.S. Federal Law restricts this device to practitioners who have been trained in its calibration and operation and who have experience in the surgical management and treatment of refractive errors.

CAUTION

Other Manuals

This addendum is only valid in conjunction with related manuals. Read this Addendum Procedure Manual and all related manuals of the laser system and its approved accessories carefully before starting to use the ALLEGRETTO WAVE® EYE-Q laser system. The system user alone is responsible for having sufficient medical knowledge for carrying out all surgical procedures.

NOTICE TO USERS There are no rightful claims to system upgrades in the event of the introduction of product improvements based on new technological developments.

Table Of Contents


TABLE OF CONTENTS Page

1. DEVICE DESCRIPTION .....................................................................................8

2. INDICATIONS, CONTRAINDICATIONS, WARNINGS, ......................................9

2.1. Indications For Use...............................................................................9

2.2. Contraindications ..................................................................................9

2.3. Warnings ............................................................................................ 10

2.4. Precautions ........................................................................................ 11

2.5. Patient Selection ................................................................................ 13

3. PROCEDURE ................................................................................................... 14

3.1. Procedure Steps ................................................................................. 14

3.1.1 Patients Preparation And Surgery ............................................................ 15

3.2. Treatment Interruption ........................................................................ 16

3.3. Ablation Details .................................................................................. 17

3.4. Typical Treatment Profiles .................................................................. 18

3.5. Optical Zones ..................................................................................... 18

3.6. Post Procedure ................................................................................... 19

4. STUDY DATA ................................................................................................... 20

4.1. Study Design ...................................................................................... 20

4.2. Study Objective .................................................................................. 21

4.3. Data Analysis ..................................................................................... 21

Table Of Contents


Page

4.4. Effectiveness Results ......................................................................... 26

4.5. Safety Results .................................................................................... 33

4.6. Patient Reported Outcomes ............................................................... 43

4.7. Overall Conclusion ............................................................................. 46

5. PREPARATION OF DEVICES, INSTRUMENTS AND MATERIAL ................. 47

6. TREATMENT PLANNING AND DATA ENTRY ................................................ 48

6.1. Treatment Plan And Data Entry .......................................................... 48

6.2. Parameters Determining Ablation ....................................................... 49

6.3. Feasibility Checks .............................................................................. 50

6.4. Ablation Depth And Remaining Stromal Thickness ............................ 51

6.5. Confirm And Save Data ...................................................................... 51

Device Description


1. DEVICE DESCRIPTION Intended Use:

The refractive laser ALLEGRETTO WAVE® EYE-Q is a stationary scanning-spot excimer laser system used in refractive surgery for Laser In-Situ Keratomileusis (LASIK) as well as for photorefractive treatments including Photorefractive Keratectomy (PRK) as described in chapter 2.1 “Indications For Use” on page 9.

The excimer laser creates a radiation of 193 nm wavelength. This radiation is able to ablate corneal tissue in very thin layers without damage or thermal alteration of collateral tissue. The ablation effect is threshold dependent - the energy per irradiated area, known as Fluence, has to be above a certain threshold to ablate corneal tissue. Below the threshold the radiation will cause heating instead of ablation.

The laser radiation is used to change the front shape of the corneal lens by ablating tissue. This sculpting has to be done with very high precision in order to achieve a new corneal lens shape with the desired smoothness of surface and precision of optical power. Every single laser pulse (spot) has to meet very high requirements regarding precision of ablated depth, volume and spot position.

The ALLEGRETTO WAVE® EYE-Q laser system consists of a combination of features including several internal energy control mechanisms and external test procedures to provide the right energy and fluence per laser pulse. The fast eyetracker for determining eye position and a precise scanner motor for positioning the laser spot enable precise placement of every laser spot even when the eye is moving or having saccades. In addition, the eyetracker offers an automatic centration of the ablation to avoid unintended decentration of the correction zone.

The Gaussian shaped energy distribution within the laser beam and a small ablation spot of approximately 1 mm assure the desired contour precision and high surface smoothness of the newly shaped corneal curvature. The ablation profiles that are used in the ALLEGRETTO WAVE® EYE-Q are “Wavefront Optimized” meaning that the initial profiles, which can be calculated mathematically, were refined by empirical research with a wavefront aberrometer.

Due to the small spot diameter used in the ALLEGRETTO WAVE® EYE-Q, the excimer laser beam source is compact with low laser gas volume and minimal laser gas consumption.

The ALLEGRETTO WAVE® EYE-Q Excimer laser system 400 Hz uses a small laser beam to reshape the cornea and treat refractive vision problems, such as nearsightedness with or without astigmatism. This excimer laser system is approved in the United States to perform LASIK (laser-assisted in situ keratomileusis) treatment, where a thin flap is created in the cornea, the laser reshapes the inner layers of the cornea after the flap is lifted, and then the flap is repositioned.

With PRK, there is no flap created. The corneal epithelium is removed with techniques including manual blade scrape, amoils brush and dilute alcohol assisted. Then the laser is applied to reshape the cornea. This laser, which delivers a cool pulsing beam of ultraviolet light, is used on the surface of the cornea and not underneath a flap made in the cornea, as in LASIK.

Indications, Contraindications, Warnings,


2. INDICATIONS, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, AND PATIENT SELECTION

2.1. Indications For Use The ALLEGRETTO WAVE® EYE-Q laser system is indicated for use in Photorefractive Keratectomy (PRK) treatments for:

• the reduction or elimination of up to - 6.0 diopters (D) of spherical equivalent myopia or myopia with astigmatism, with up to - 6.0 D of spherical component and up to - 3.0 D of astigmatic component at the spectacle plane,

• patients who are 18 years of age or older and

• patients with documentation of a stable manifest refraction defined as ≤ 0.5 D preoperative spherical equivalent shift over one year prior to surgery.

2.2. Contraindications PRK treatments using the ALLEGRETTO WAVE® EYE-Q laser are contraindicated if any of the following conditions exist. Potential contraindications are not limited to those included in this list:

• progressive myopia with or without astigmatism, acute or recurrent ocular disease, previous corneal or intraocular surgery, or trauma in the ablation zone,

• patients with a weakened immune system, including diagnosed collagen vascular, atopic syndrome, autoimmune or immunodeficiency disease,

• patients with degeneration of structures of the cornea, diagnosed keratoconus or any clinical pictures suggestive to keratoconus,

• patients with recurrent corneal erosion. This condition can lead to serious corneal problems during and after PRK.

• patients with uncontrolled diabetes,

• patients with a thin cornea and which is not thick enough to undergo the necessary ablation for the PRK procedure,

• patients with uncontrolled glaucoma. It is unknown whether PRK is safe and effective for such patients.

• patients with eyes that have a calculated residual stromal bed thickness that is less than 250 microns, and

• patients with severe dry eyes.

• Eyes with unstable visual acuity by manifest refraction (change of more than 0.5 diopter in myopia or astigmatism) over the prior 12 months preceding surgery.

• Herpes (herpes simplex or herpes zoster) eye infection within the past year or corneal damage from prior herpes eye infections.



2.3. Warnings Any PRK treatment with the ALLEGRETTO WAVE® EYE-Q is not recommended in patients who have:

• systemic diseases likely to affect wound healing, such as connective tissue disease, insulin dependent diabetes, severe atopic disease or an immunocompromised status,

• controlled autoimmune or connective tissue disease,

• significant dry eye that is unresponsive to treatment,

• uncontrolled or untreated eye allergies,

• controlled glaucoma, ocular hypertension, or being followed for possible glaucoma (glaucoma suspect),

• taking the medication Isotretinoin (Accutane®1).

• patients with controlled diabetes • Patients with weakened immune system • Patients with history of eye injury and eye pain • Patients with history of strabismus • Patients with decreased vision in one eye

A complete examination, including, but not limited to cycloplegic evaluation must be performed. Direct and indirect ophthalmoscopy through a dilated pupil is essential. Evaluation of the optic nerve and measurement of IOP are necessary. If there are any concerns regarding the appearance of the optic nerve, a threshold test of the visual field should be performed. Baseline evaluation of patients with myopia desiring refractive surgery should be performed within 30 days prior to PRK surgery.

1 Accutane® is a registered trademark of Hoffmann-La Roche Inc.



2.4. Precautions Safety and effectiveness of the ALLEGRETTO WAVE® EYE-Q laser system for PRK treatments has not been established for patients with:

• corneal abnormalities including, but not limited to, scars, irregular astigmatism and corneal warpage,

• with history of glaucoma or ocular hypertension of > 23 mmHg,

• taking the medication sumatriptan succinate (Imitrex®2),

• taking the medication amiodarone hydrochloride (Cordarone®3),

• under 18 years of age,

• over the long term (more than 12 months after surgery),

• corneal, lens and/or vitreous opacities including, but not limited to cataract,

• corneas that are too thin,

• iris problems including, but not limited to, coloboma and previous iris surgery compromising proper eye tracking,

• taking medications likely to affect wound healing including, but not limited to, antimetabolites,

• treatment targets different from emmetropia (plano) in which the wavefront-calculated defocus (spherical term) and the astigmatism (cylinder term) has been adjusted, additionally, physician adjustment of wavefront-calculated defocus may negate the potential benefits of the Wavefront-Guided procedure. You should discuss with your patient the potential risks and benefits associated with treatment targets different from emmetropia.

• myopia with or without astigmatism that is not within the FDA-approved treatment range of - 6.0 D MRSE, up to - 6.0 D sphere, or up to - 3.0 D cylinder,

• any other medical condition that might be expected to make the patient an unsuitable candidate for PRK treatment,

• large pupils,

• with severe allergies or eye rubbing condition

• with undiagnosed dry eyes, and

• PRK will also cause difficulties with future health:

o future IOP measurements

o future cataract surgery

• pregnant or nursing women

2 Imitrex® is a registered trademark GlaxoSmithKline Inc. 3 Cordarone® is a registered trademark of Wyeth Inc.



If there is an infection or problem with healing after the surgery, it is more likely that both eyes will be affected if both eyes are treated at the same session. If only one eye is treated, the difference in vision between the treated eye and the one without treatment might make vision difficult. In such a case, the patient might not have functional vision unless the second eye is treated with PRK or by wearing glasses or contact lenses that compensate for the difference. Pupil sizes should be evaluated under mesopic illumination conditions. Effects of treatment on eyes under poor illumination cannot be predicted prior to surgery. Some patients may find it more difficult to see in such conditions as very dim light, rain, fog, snow and glare from bright lights. This has been shown to occur more frequently in the presence of residual refractive error and perhaps in patients with pupil sizes larger than the optical zone size. The refraction is determined in the spectacle plane, but treated in the corneal plane. In order to determine the right treatment program to achieve the right correction, assessment of the vertex distance during refraction test is recommended. Preoperative evaluation for dry eyes must be performed. Patients should be advised of the potential risk for dry eyes post PRK surgery.



2.5. Patient Selection In addition to contraindications, precautions and warnings the following should be considered and discussed with your patient in order to find good candidates for PRK and to get sufficient information for the treatment plan:

• A complete baseline exam including, but not limited to, cycloplegic refraction within 60 days prior to surgery is necessary.

• A slit lamp exam has to be performed. The status of the lens has to be evaluated to ensure that neither nuclear sclerosis nor other lens opacities are present. These opacities may adversely affect final visual result.

• Dilated fundus exam by indirect ophthalmoscopy has to be performed, as retinal pathology is more likely in patients with myopia.

• Optical nerve and intraocular pressure have to be examined, as glaucoma is more common in myopic than emmetropic patients. If elevated pressure or signs of glaucomatous damage are found, topical steroids should be used only under careful medical supervision or the patient should not be treated.

• In order to exclude corneal abnormalities careful videokeratography (topography) is essential.

• Contact lens wearers must discontinue wearing hard or gas permeable lenses for at least 3 weeks and soft lenses for at least 1 week prior to preoperative evaluation.

• Contact lens wearers must also discontinue wearing hard or gas permeable lenses for at least 3 weeks and soft lenses for at least 1 week prior to surgery.

• The patient must be able to lie flat in a supine position.

• Topical or local anesthesia must be tolerated.

• The patient must be able to fixate steadily.

• The patient must be able to understand and give the informed consent and sign the consent form.

• All alternatives to the PRK procedure for correcting myopia with or without astigmatism by spectacles, contact lenses and other surgical procedures such as LASIK, radial keratotomy, automated lamellar keratoplasty or clear lens exchange should be clearly communicated and understood by the patient.

• Additionally patients should be instructed not to wear makeup at the day of surgery. Patients must not use perfumes, aftershave, Eau de Cologne or other substances applied to the skin containing alcohol at that day.

• Patients with heart pacemakers may not be treated

Procedure


3. PROCEDURE

3.1. Procedure Steps The determined patient and eye data have to match with the patient presenting and with the eye prepared for surgery. Make sure that treatment parameters are precisely transferred from the files to the laser system. A double check with the patient and assisting personnel is recommended. It is the sole responsibility of the operating surgeon to ensure that all data is accurate.

The corneal epithelium should be removed, with a total epithelium removal diameter of approximately 9.0 mm. Methods of removal include manual blade scrape, Amoils brush, or dilute alcohol-assisted.

Instruct patients not to wear makeup as this poses risk for contamination of the stromal interface. Patients must not use perfumes, after shave, eau de cologne or other substances applied to the skin containing alcohol.

Aromatic substances and solvents including, but not limited to alcohol, fresh glue and paint should not be noticeable at the laser aperture. Vapors of all such substances absorb energy of the laser pulses and therefore may cause undercorrections.

Strong disturbances of the air between the laser aperture and the patient’s head during laser ablation must be avoided. Switch off any ventilation device causing a noticeable airflow during ablation, with exception of the plume evacuator of the laser system. Instruct personnel not to move around and keep doors and windows closed during ablation. Uncontrolled airflow may have an effect on the quality of the ablation.

Potentially noisy devices such as telephones that may cause a sudden sound during the procedure should be switched off. Sudden noise may distract surgeon and / or patient.

Medications likely to dilate or constrict the pupil should be administered with careful supervision during the last 6 hours prior to surgery as the eyetracker will not be able to track pupils of less than 1.5 mm and more than 8.0 mm diameter. Furthermore, such medication might influence the physiological center of the pupil and compromise centration of the eye tracking system.

Check that the patient is able to see the green blinking fixation light and to distinguish it from other light sources around the laser aperture.

Perform an External Energy Check according to the Operator’s Manual prior to treating a new patient. The cross-line projector can be used to align the patient’s head position, but must be switched off during the course of the ablation process.

Repeat the test if more than 30 minutes have elapsed before the treatment is begun.

Head alignment in order to apply cylinder treatment in the right axis is essential.

The ablation treatment is triggered by pressing the LASER foot pedal. It can be interrupted at any time by leaving the pedal. The laser will stop automatically when the treatment process is finished.

Procedure


3.1.1 Patients Preparation And Surgery Place patient’s arms on patient’s belly or aside the body. Instruct patient not to move his or her arms for duration of procedure. Place pillow below patient’s knee joint for better comfort. Have patient confirm that position is comfortable. Perform asepsis around the eye(s) and drape the eye according to your preferred method. Move patient under the laser arm by pushing the Auto Positioning Button at the bed. Figure 1: Auto Position Button Swing Eyetracker Illumination out - not fully, just over the patient’s throat. Mark the 0°-Axis on the sclera at the slit lamp with a gentaviolet marker. Position the patients head roughly under the microscope. Adjust the focus with the distance diodes. Switch on the cross line projector and adjust the brightness to your personal needs. Adjust the patient’s head that the horizontal line of the cross line projector correlates with the marks at the sclera. The vertical line must be in the center of the pupil. Figure 2: Marked Sclera Switch off the cross line projector.

Procedure


CAUTION

Aborted Treatment

The laser system offers no assistance to finish a treatment at a later time if it had been aborted. Consult a clinical application specialist of WaveLight GmbH to discuss possible options.

3.2. Treatment Interruption If laser ablation is interrupted, the parameters remain in the system and the system will proceed with the ablation pattern exactly at that point, at which the treatment was interrupted. The progress of the ablation procedure is indicated in the LCD screen of the laser console. Figure 1: Progress Indicators If for any reason a treatment has to be terminated before ablation is completed, the percentage of treatment accomplished has to be recorded and kept in the patient files.

Procedure


3.3. Ablation Details During ablation spherical and astigmatic error are treated separately. The spherical portion of the refractive treatment is applied first, the astigmatic portion follows immediately without interruption. In myopic treatments both ablation portions are enrolled by creating the full amount of intended correction during the first few seconds, but in a diameter smaller than the full optical zone. During the course of the ablation the zone already corrected is enlarged to the programmed optical zone diameter. The currently achieved diameter with full correction is not indicated. Please note that the treatment progress indicated by the software is neither related to the amount of ablated diopters, nor to a certain ablation zone. Figure 2: Evolution Of Ablation Myopic Treatment Myopic astigmatism treatments flatten the axis of the (positive) cylinder. Keep the stromal surface dry and clean during ablation. Prevent liquid or blood from running towards the ablation zone. Liquid and debris will shield the stromal surface against ablation. Irregular ablations will most likely result. If liquid or blood reaches the optical zone area, irregular ablations may lead to deviation of the best possible clinical results. Do not move instruments across or in the area of the intended optical zone during laser ablation. The instrument may shield stroma partially against ablation. Resulting irregular ablations may lead to a deviation of the best possible clinical result. Optical zones are always circular. The ablation zone shape depends on treatment type. Optical and ablation zone diameters are indicated in the notebook computer screen. The LCD screen of the laser console shows the optical zone diameter only. Avoid shadowing of any of the three infra-red illumination spots during registration and ablation, as this might cause interference to the detection of the pupil and centration.

Procedure


3.4. Typical Treatment Profiles The following figures show typical ablation depth profiles for myopic spherical and cylindrical treatments (the higher the profile or the “hotter” the color, the deeper the ablation). Figure 3: Myopic Ablation Depth Profiles For Sphere (Left), Cylinder (Middle) And Spherocylinder (Right)

3.5. Optical Zones The optical zone is the area where the intended correction treatment is applied. Optical zones treatments are circular for all types of treatments. They are surrounded by a blend zone, called transition zone. Both add up to the ablation zone. The ablation zone determines the area hit by laser pulses. The shape of transition and ablation zone varies due to the type of treatment. Ablation zones of myopic spheres are circular. Ablation zones of myopic cylinders are elliptical. Figure 4: Optical And Ablation Zone Myopic Treatments

Procedure


3.6. Post Procedure The following post-operative examinations are recommended on day 1 or 2 and at 1, 3 and 6 months: Slit Lamp Examination, Uncorrected Visual Acuity (UCVA or VA sc), Best Spectacle-Corrected Visual Acuity (BSCVA or VA cc), Manifest Refraction, Intraocular Pressure at 3 months or at any post-operative date later than 2 weeks after surgery, if patient’s vision has deteriorated significantly within days and Keratometry and Videokeratography at 1, 3 and 6 months. After ablation, the eye presently operated on should be irrigated with a balanced salt solution (BSS). A bandage contact lens can be used on the treated eye until re-epithelialization has occurred. Antibiotics and steroid anti-inflammatory drops may be used after treatment as needed. Ocular or oral pain medications may be prescribed for early postoperative pain management. Postoperative follow-up should occur, at minimum, the first day after surgery and very day until the re-epithelialization is complete.

Study Data


4. STUDY DATA

4.1. Study Design This study was a prospective, multi-center, single group, safety and effectiveness study conducted at eight (8) clinical sites in the US. A total of 320 eyes with myopia, with or without astigmatism, had photorefractive keratectomy (PRK) with the ALLEGRETTO WAVE® EYE-Q excimer laser system. Subjects who agreed to participate in the clinical study provided informed consent and underwent the required screening procedures to determine study eligibility. Subjects in whom at least one eye had a preoperative refractive error within the specified range (Sphere and MRSE up to - 6.0 D and cylinder up to -3.0 D) and met all study eligibility criteria had PRK. Corneal topography, pachymetry, keratometry, pupillometry, aberrometry, manifest refraction and measurements of uncorrected visual acuity (UCVA) were obtained at baseline and at scheduled times after PRK to evaluate study eligibility and/or effectiveness of the treatment. Safety monitoring throughout the study included adverse event reporting at scheduled and unscheduled visits, contrast sensitivity, clinically significant findings from dilated fundus and slit lamp examinations and measurements of best spectacle corrected visual acuity (BSCVA) at baseline and at scheduled times after PRK. Subjects completed questionnaires to evaluate subjective visual complaints prior to and after PRK. Treatment planning was done with Wavefront Optimized profiles. The laser software used the nomogram adjusted manifest refraction data to determine the treatment plan for PRK. All eyes were targeted for emmetropia.

Study Data


4.2. Study Objective The purpose of this study was to evaluate the safety and effectiveness of PRK (Photorefractive Keratectomy) for myopia with or without astigmatism using the ALLEGRETTO WAVE® EYE-Q excimer laser system.

4.3. Data Analysis The intent-to-treat (ITT) data set was the primary dataset for the effectiveness analyses. All subjects who underwent surgery were included in the ITT data set. The safety dataset was the dataset used for all safety analyses. All subjects enrolled in the study who underwent a surgical procedure (any instrument touches the eye in the operating room) were included in the safety dataset. Safety and effectiveness cohorts may differ in number depending on the availability of data at each time point of analysis. Subject disposition is presented in Table 1 for the 176 subjects that enrolled (signed informed consent) in the study. Fifteen subjects did not meet inclusion and exclusion criteria and were considered screen failures. A total of 161 subjects were treated. For 2 subjects, only 1 eye was treated (the fellow eye did not qualify). Nine subjects discontinued from the study.

Table 1: Subject Disposition (All Enrolled)

n (%) Enrolled 176 Screen Failures 15 Treateda 161 (100.0) Completed Study 152 (94.4) Discontinued 9 (5.6) Lost to Follow-up 7 (4.3) Unable to Make Future Office Visits 2 (1.2) n = Number of subjects in category a Subjects 1001 and 1002 had only one eye treated.

Study Data


Demographic characteristics of the subjects enrolled in the study are summarized in Table 2. The age of the subjects ranged from 18 to 64 years, with a mean age of 31.5 years at the time of screening. The subject population consisted of a similar percentage of male (44.7%) and female (55.3%) subjects and was predominantly white (78.3%) of non-Hispanic or Latino ethnicity (88.8%).

Study Data


Preoperative baseline characteristics included manifest refraction sphere, manifest refraction cylinder, MRSE (manifest refraction spherical equivalent), UCVA (uncorrected visual acuity) in logMAR, and BSCVA (best spectacle corrected visual acuity) in logMAR. Table 3 presents the summary statistics for the baseline characteristics by eye.

Table 3: Baseline Characteristics by Eye (Intent-to-Treat)

Baseline Characteristic Statistic Results Manifest Sphere n 320 Mean -2.957 SD 1.4843 Median -2.75 (Min, Max) (-6.00, -0.25) 95% CI (-3.120, -2.794)

Manifest Cylinder n 320 Mean -0.788 SD 0.8191 Median -0.50 (Min, Max) (-3.00, 0.00) 95% CI (-0.878, -0.697)

MRSE n 320 Mean -3.351 SD 1.4191 Median -3.25 (Min, Max) (-6.00, -0.75) 95% CI (-3.507, -3.195)

UCVA n 320 Mean 0.870 SD 0.2656 Median 0.92 (Min, Max) (0.28, 1.40) 95% CI (0.841, 0.900)

BSCVA n 320 Mean -0.085 SD 0.0741 Median -0.10 (Min, Max) (-0.28, 0.12) 95% CI (-0.093, -0.076)

n = Number of eyes in ITT analysis set with data SD = Standard deviation, Min = Minimum, Max = Maximum CI = Confidence Interval MRSE = Manifest refraction spherical equivalent UCVA = Uncorrected visual acuity BSCVA = Best-spectacle corrected visual acuity

Study Data


The preoperative bin distribution based on the preoperative manifest refraction is summarized in Table 4, with stratification based on sphere and cylinder. An adequate number of eyes were treated in each sphere and cylinder bin. Accountability by eye is summarized in Table 5. There was good accountability in this study with a high percentage of eyes that were available for analysis, ranging from 97.2% to 100%, with the lowest percentage at Month 12.

Study Data


Table 6 presents the MRSE and manifest refractive cylinder results. The time point of refractive stability was established at Month 6 (Visit 8) because the following criteria were met for the Month 3 to Month 6 interval:

• 99.7% and 100% of eyes had a change of MRSE and manifest refractive cylinder of ≤ 1.0 D, respectively

• The mean rate of change per year was -0.019 D and 0.038 D for MRSE and manifest refractive cylinder respectively

• The 95% confidence interval for the mean rate of change included zero

• The mean rate of change decreased towards zero over time, although there was clinically non-significant increase or decrease in mean change in MRSE and manifest refractive cylinder between consecutive intervals over time

• The refractive stability criteria were confirmed for the Month 6 to Month 9 interval

Study Data


4.4. Effectiveness Results A total of 299 eyes with pre-operative best spectacle-corrected visual acuity (BSCVA) of 20/20 or better participated in the study. The primary effectiveness objectives were:

• To demonstrate that, at refractive stability, the percentage of eyes that achieve uncorrected visual acuity (UCVA) of 20/40 or better (in eyes with best spectacle corrected visual acuity (BSCVA) 20/20 or better preoperatively) would be equal to or greater than 85%

• To demonstrate that 95% of eyes would have a change of ≤ 1.0 diopter (D) in manifest refraction spherical equivalent (MRSE) and manifest refractive cylinder between 2 refractions, performed at 1 and 3 months postoperatively, or over a minimum 3 month period thereafter

• To demonstrate that, at refractive stability, the percentage of eyes achieving MRSE within ± 1.0 D of target emmetropia would be equal to or greater than 75%

• To demonstrate that, at refractive stability postoperatively, the percentage of eyes achieving manifest refractive cylinder within ± 1.0 D of zero would be equal to or greater than 75%


• To demonstrate that, at refractive stability, the percentage of eyes achieving manifest refractive cylinder within ± 0.5 D of zero would be equal to or greater than 50%

The proportion of eyes that met the visual and refractive outcome criteria is summarized in Table 7. These results are that at Month 6:

• 100% of eyes with preoperative BSCVA of 20/20 or better achieved UCVA of 20/40 or better

• 99.7% of eyes achieved MRSE within ± 1.0 D of zero


• 99.0% of eyes achieved manifest refractive cylinder within ± 1.0 D of zero

• 92.7% of eyes achieved MRSE within ± 0.5 D of zero The results after Month 6 are consistent or slightly better than the results at Month 6.

Study Data


As shown in Table 8, a change of ≤ 1.0 D in MRSE and manifest refractive cylinder between 2 refractions performed at 1 and 3 months postoperatively or over a minimum 3-month period thereafter was observed for 95.6% of eyes. Furthermore, within the interval that included the time point of refractive stability (between Month 6 to Month 9 visits), a change of ≤ 1.0 D in MRSE and manifest refractive cylinder was observed in 99.7% of eyes.

Table 7: Proportion of Eyes Meeting Visual and Refractive Outcome Criteria (Intent-to-Treat)

Visit Parameter n / N (%) 95% CI† Visit 5 - Week 1 UCVA 20/40 or better (BSCVA 20/20 or better pre-op) 270 / 299 (90.3) (86.4, 93.4) MRSE within ± 1.00 D of emmetropia 307 / 320 (95.9) (93.2, 97.8) MRSE within ± 0.50 D of emmetropia 255 / 320 (79.7) (74.9, 84.0) Manifest refractive cylinder within ± 1.00 D of plano 296 / 320 (92.5) (89.0, 95.1) Manifest refractive cylinder within ± 0.50 D of plano 250 / 320 (78.1) (73.2, 82.5)

Visit 6 - Month 1 UCVA 20/40 or better (BSCVA 20/20 or better pre-op) 293 / 299 (98.0) (95.7, 99.3) MRSE within ± 1.00 D of emmetropia 312 / 320 (97.5) (95.1, 98.9) MRSE within ± 0.50 D of emmetropia 258 / 320 (80.6) (75.9, 84.8) Manifest refractive cylinder within ± 1.00 D of plano 303 / 320 (94.7) (91.6, 96.9) Manifest refractive cylinder within ± 0.50 D of plano 239 / 320 (74.7) (69.6, 79.4)





N = Number of eyes in ITT analysis set with data at visit n = Number of eyes in category † 95% confidence interval from Binomial distribution

Study Data


Study Data


Table 9 presents the results for eyes that achieved UCVA of 20/20 or better and 20/40 or better. At Month 6, 93.0% of eyes had UCVA of 20/20 or better and 100% of eyes had UCVA of 20/40 or better. Similar results were seen after Month 6.

Study Data


The summary of the non-vector results of MRSE and visual acuity at Month 6 are presented in Table 10. All eyes had MRSE within ± 2.0 D of zero. The percentage of eyes undercorrected by greater than 1.0 D MRSE was low at 0.3%; no eyes were overcorrected by more than 1.0 D MRSE. The majority of eyes (68.5%) had UCVA better than or equal to their preoperative BSCVA. Finally, no eyes showed a decrease from baseline in BSCVA of 2 lines or greater. Table 10: Non-Vector Analyses by Eye at Stability Time Point (Month 6) (Intent-to-Treat) Parameter n / N (%) 95% CI† MRSE ± 2.00 D of emmetropia 314 / 314 (100.0) (98.8, 100.0) Overcorrected by > 1.00 D MRSE 0 / 314 (0.0) (0.0, 1.2) Overcorrected by > 2.00 D MRSE 0 / 314 (0.0) (0.0, 1.2) Undercorrected by > 1.00 D MRSE 1 / 314 (0.3) (0.0, 1.8) Undercorrected by > 2.00 D MRSE 0 / 314 (0.0) (0.0, 1.2) UCVA equal to or better than preoperative BSCVA Difference in postoperative and preoperative BSCVA

215 / 314 (68.5) (63.0, 73.6)

< -2 lines 3 / 314 (1.0) (0.2, 2.8) -2 lines 7 / 314 (2.2) (0.9, 4.5) -1 line 83 / 314 (26.4) (21.6, 31.7) 0 lines 218 / 314 (69.4) (64.0, 74.5) 1 line 3 / 314 (1.0) (0.2, 2.8) 2 lines 0 / 314 (0.0) (0.0, 1.2) > 2 lines 0 / 314 (0.0) (0.0, 1.2) N = Number of eyes in ITT analysis set with data at visit n = Number of eyes in category † 95% confidence interval from Binomial distribution

Study Data


Table 11 presents the results for the accuracy of cylinder to target in eyes that had preoperative astigmatism. At Month 6, 98.7 % of eyes were within ± 1.0 D of cylinder target (zero), and 91.1% were within ± 0.5 D of cylinder target.

Table 11: Accuracy of Cylinder to Target by Eye (Intent-to-Treat)

Cylinder Visit 1

Screening Visit 6

Month 1 Visit 7

Month 3 Visit 8

Month 6 Visit 9

Month 9 Visit 10

Month 12 No. Eyes (N) 230 230 227 224 224 223 Mean ± SD -1.096 ± 0.77 -0.393 ± 0.43 -0.227 ± 0.30 -0.209 ± 0.29 -0.185 ± 0.28 -0.179 ± 0.29 Attempted change ± SD 1.096 ± 0.77 Achieved change ± SD 0.702 ± 0.90 0.866 ± 0.78 0.886 ± 0.78 0.910 ± 0.77 0.904 ± 0.76 % of eyes within ± 0.50 D of target

69.1 90.3 91.1 94.2 94.2

% of eyes within ± 1.00 D of target

93.0 98.7 98.7 98.7 98.7

N = Number of eyes with preoperative cylindrical component with data at visit SD = Standard deviation

Study Data


Results of the vector analyses at Month 6 are presented in Table 12. The mean error vector (EV), defined as the vector difference between the intended refractive correction and the surgically induced refractive correction (IRC - SIRC), was low (< 0.2), indicating a low postoperative astigmatic correction vector. The mean correction ratio (CR), which is the ratio of the achieved correction magnitude to the required correction magnitude, was close to the ideal of 1 in each preoperative cylinder category. Error ratio (ER), defined as the proportion of the intended correction that was not successfully treated, was small in each preoperative cylindrical category, and showed a progressive decrease in mean with increasing preoperative cylinder.

Table 12: Vector Analysis Summary at Stability Time Point (Month 6) (Intent-to-Treat)

Preoperative Cylinder n

|IRC| (Mean ± SD)

|SIRC| (Mean ± SD)

|EV| (Mean ± SD)

CR (Mean ± SD)

ER (Mean ± SD)

All Eyes (N) 224 1.013 ± 0.7161 1.130 ± 0.7722 0.159 ± 0.2449 1.180 ± 0.4493 0.229 ± 0.4261 0.0 D to 0.5 D 89 0.397 ± 0.1075 0.502 ± 0.2241 0.120 ± 0.1943 1.302 ± 0.5989 0.343 ± 0.5763 >0.5 D to 1.0 D 54 0.808 ± 0.1186 0.908 ± 0.3467 0.174 ± 0.2664 1.115 ± 0.4018 0.216 ± 0.3570 >1.0 D to 2.0 D 50 1.450 ± 0.2240 1.628 ± 0.3866 0.189 ± 0.2827 1.122 ± 0.1950 0.129 ± 0.1899 >2.0 D to 3.0 D 31 2.434 ± 0.2510 2.514 ± 0.4194 0.198 ± 0.2670 1.033 ± 0.1450 0.085 ± 0.1209 n = Number of eyes with preoperative cylindrical component with data at visit SD = Standard deviation, Min = Minimum, Max = Maximum IRC = Intended Refractive Correction, SIRC = Surgically Induced Refractive Correction, EV = Error Vector, CR = Correction Ratio, ER = Error Ratio

Study Data


4.5. Safety Results The primary safety objectives of this study were:

• To demonstrate that the observed rate of each type of ocular serious adverse event (SAE) would be no more than 1%

• To demonstrate that the percentage of eyes with BSCVA decrease of ≥ 2 lines from baseline would be less than 5% at refractive stability

• To demonstrate that the percentage of eyes with a BSCVA worse than 20/40 (for eyes with BSCVA of 20/20 or better preoperatively) would be less than 1% at refractive stability

• To demonstrate that the percentage of eyes with > 2.00 D of induced manifest refraction cylinder magnitude as compared to baseline would be less than 5% at refractive stability

The following ocular serious adverse events were defined in the protocol and reported:

• Corneal infiltrate or ulcer

• Any persistent corneal epithelial defect at 1 month or later

• Corneal edema at 1 month or later

• IOP with increase of > 10 mmHg above baseline on 2 consecutive examinations or an

• IOP greater than 30 mmHg on 2 consecutive examinations

• Haze beyond 6 months with loss of 2 lines or greater (≥ 10 letters ETDRS) of BSCVA

• Decrease in BSCVA of greater than or equal to 2 lines (≥ 10 letters ETDRS) not due to irregular astigmatism as shown by rigid contact lens refraction at 3 months or later

• Retinal detachment

• Retinal vascular accidents

• Any other vision-threatening event

• Ocular penetration

Study Data


The cumulative rate of SAEs is presented in Table 13. The observed rate of any SAE event type was less than 1%, achieving one of the co-primary safety objectives. The corneal infiltrate events occurred at 1 day after PRK and resolved with medications. The corneal edema event occurred at approximately 5 months after PRK and resolved without treatment. All events were assessed as being unrelated to the device and related to the PRK procedure.

Study Data


Results of other co-primary safety outcomes are presented in Table 14. All co-primary safety results achieved the target rates at Month 6. No eyes had BSCVA decrease of ≥ 2 lines from baseline, or BSCVA worse than 20/40 (in eyes with BSCVA of 20/20 or better preoperatively), or > 2.00 D of induced manifest refraction cylinder compared to baseline. Similar results were seen after Month 6.

Table 14: Best Spectacle Corrected Visual Acuity and Manifest Cylinder by Eye (Intent-to-Treat)

Visit Parameter n / N (%) 95% CI† Visit 5 - Week 1 BSCVA decrease of 2 line s from ba s e line 80 / 320 (25.0) (20.4, 30.1) BSCVA worse than 20/40 (BSCVA 20/20 or better preop) 8 / 299 (2.7) (1.2, 5.2) Increase of > 2.00 D of induced manifest refraction cylinder 0 / 320 (0.0) (0.0, 1.1)

Visit 6 - Month 1 BSCVA decrease of 2 line s from ba s e line 13 / 320 (4.1) (2.2, 6.8) BSCVA worse than 20/40 (BSCVA 20/20 or better preop) 0 / 299 (0.0) (0.0, 1.2) Increase of > 2.00 D of induced manifest refraction cylinder 0 / 320 (0.0) (0.0, 1.1)






Study Data


The following ocular non-serious adverse events were defined in the protocol and reported:

• Corneal edema between 1 week and 1 month after the procedure

• Peripheral corneal epithelial defect at 1 month or later

• Recurrent corneal erosion at 1 month or later

• Foreign body sensation at 1 month or later

• Pain at 1 month or later

• Ghost/double images in the operative eye

• Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later which the investigator has determined is not easily resolved when the subject is wearing correction or has some simple explanation unrelated to the treatment. The investigator should use his medical judgment to determine if one or both eyes are experiencing the symptom marked moderate or severe (e.g. Examine slit lamp findings) and document this on the adverse event case report form. Justification should be provided on the comments case report form if the symptom is not considered an AE

• Clinical signs consistent with marked to severe dry eye at 6 months or later

• Any symptoms of dry eye that significantly affect comfort or activities of daily living

• (as reported to the investigator) at 6 months or later

• Any symptoms of glare or haloes that significantly affect comfort or activities of daily

• living (as reported to the investigator) at 6 months or later Table 15 presents the rates of non-serious protocol-specified AEs for only those participants with a “moderate” or “severe” VSARC questionnaire result (foreign body sensation, ghosting/double images, pain). As shown in tables 16 and 17, these adverse events were mostly mild in severity and the majority resolved by 12 months postoperative. Within the AE category of “Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later”, 4.1% of eyes had pain, 4.4% of eyes had foreign body sensation, and there were no reports of ghost or double images. The overall rate of “Any symptom marked moderate or severe on the VSARC questionnaire at Month 6 or later” was 18.4%. Within this category, the highest rates were observed for dryness in eyes (10.9%), eyes sensitive to light (5.9%), foreign body sensation (4.4%) and pain in eyes (4.1%).

Study Data


Table 15: Cumulative Incidence of Non-Serious Protocol-Specified Adverse Events by Eye, (Intent-to-Treat)

(N=320) Adverse Event n (%) E Recurrent corneal erosion at 1 month or later 3 (0.9) 3 Any symptoms of dry eye that significantly affect comfort or activities of daily living at 6 months or later 64 (20.0) 64 Any symptoms of glare or haloes that significantly affect comfort or activities of daily living at 6 months or later 14 (4.4) 18 Clinical signs consistent with marked to severe dry eye at 6 months or later 1 (0.3) 1 Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later 59 (18.4) 128 1 - Pain in eyes 13 (4.1) 13 2 - Dryness in eyes 35 (10.9) 35 3 - Burning feeling in eyes 10 (3.1) 10 4 - Glare 2 (0.6) 2 5 - Eyes sensitive to light 19 (5.9) 19 6 - Halos (circle shapes around lights) 10 (3.1) 10 7 - Starbursts (star shapes around lights) 4 (1.3) 4 8 - Blurry vision 6 (1.9) 8 10 - Fluctuation (changes) in vision 6 (1.9) 6 11 - Difficulty focusing in dim or low light 2 (0.6) 2 12 - Watery Eyes / Tearing 5 (1.6) 5 13 - Foreign body sensation (feeling like something is in your eye) 14 (4.4) 14 Foreign body sensation at 1 month or later 23 (7.2) 29 Ghost/double images in the operative eye 30 (9.4) 31 Pain at 1 month or later 22 (6.9) 26 N = Number of eyes in ITT analysis set n = Number of eyes with events E = Number of events If an eye has multiple occurrences of an AE, the eye is presented only once in the respective count column (n) for the corresponding AE. Events are counted each time in the event (E) column. Denominators for percentages are the number of treated eyes.

Study Data


Table 16: Cumulative Incidence of Ocular Protocol Specified Adverse Event – Severity, (Intent-to-Treat)

Protocol Specified Mild Moderate Severe Adverse Event Category Adverse Event E n (%) n (%) n (%) Corneal edema between 1 week and 1 month after the procedure Corneal Oedema 1 1 (100.0) 0 ( - ) 0 ( - ) Corneal infiltrate or ulcer Corneal Infiltrates 2 2 (100.0) 0 ( - ) 0 ( - ) Recurrent corneal erosion at 1 month or later Corneal Erosion 3 2 (66.7) 1 (33.3) 0 ( - ) Any symptoms of dry eye that significantly affect comfort or activities of daily living at 6 months or later Dry Eye 64 37 (57.8) 23 (35.9) 4 (6.3) Any symptoms of glare or haloes that significantly affect comfort or activities of daily living at 6 months or later Glare 10 10 (100.0) 0 ( - ) 0 ( - ) Halo Vision 8 6 (75.0) 0 ( - ) 2 (25.0) Clinical signs consistent with marked to severe dry eye at 6 months or later Dry Eye 1 1 (100.0) 0 ( - ) 0 ( - ) Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later Dry Eye 35 12 (34.3) 19 (54.3) 4 (11.4) Eye Irritation 10 0 ( - ) 8 (80.0) 2 (20.0) Eye Pain 13 1 (7.7) 10 (76.9) 2 (15.4) Foreign Body Sensation

In Eyes 14 2 (14.3) 10 (71.4) 2 (14.3) Glarea 2 2 (100.0) 0 ( - ) 0 ( - ) Halo Visiona 10 2 (20.0) 6 (60.0) 2 (20.0) Lacrimation Increased 5 3 (60.0) 2 (40.0) 0 ( - ) Photophobia 19 2 (10.5) 15 (78.9) 2 (10.5) Photopsia 4 2 (50.0) 2 (50.0) 0 ( - ) Vision Blurreda 10 0 ( - ) 10 (100.0) 0 ( - ) Visual Impairment 6 2 (33.3) 4 (66.7) 0 ( - ) Foreign body sensation at 1 month or laterb Foreign Body Sensation

In Eyes 186 167 (89.8) 17 (9.1) 2 (1.1) Ghost/double images in the operative eyeb Diplopia 86 60 (69.8) 19 (22.1) 7 (8.1) Pain at 1 month or laterb Eye Pain 139 121 (87.1) 16 (11.5) 2 (1.4) E = Number of events n = Number of events in severity category Percentage is calculated as n/E. a The events glare (n=2, E=4), halos (n=2, E=6), and blurry vision (n=1, E=2) were reported by investigators as AEs based on VSARC responses. Although these events do not meet the protocol specified definition of “Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later”, Alcon considers that they are best accounted for in this table. b Events for these categories were identified through the VSARC questionnaire. Self-reported responses other than none were reported as adverse events.

Study Data


Table 17: Cumulative Incidence of Ocular Protocol-Specified Adverse Event – Resolution, (Intent-to-Treat)

Protocol Specified Resolved Not

Resolved Unknown Adverse Event Category Adverse Event E n (%) n (%) n (%) Corneal edema between 1 week and 1 month after the procedure Corneal Oedema 1 1 (100.0) 0 ( - ) 0 ( - ) Corneal infiltrate or ulcer Corneal Infiltrates 2 2 (100.0) 0 ( - ) 0 ( - ) Recurrent corneal erosion at 1 month or later Corneal Erosion 3 2 (66.7) 1 (33.3) 0 ( - ) Any symptoms of dry eye that significantly affect comfort or activities of daily living at 6 months or later Dry Eye 64 29 (45.3) 33 (51.6) 2 (3.1) Any symptoms of glare or haloes that significantly affect comfort or activities of daily living at 6 months or later Glare 10 6 (60.0) 4 (40.0) 0 ( - ) Halo Vision 8 4 (50.0) 4 (50.0) 0 ( - ) Clinical signs consistent with marked to severe dry eye at 6 months or later Dry Eye 1 1 (100.0) 0 ( - ) 0 ( - ) Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later Dry Eye 35 11 (31.4) 22 (62.9) 2 (5.7) Eye Irritation 10 4 (40.0) 4 (40.0) 2 (20.0) Eye Pain 13 4 (30.8) 7 (53.8) 2 (15.4) Foreign Body Sensation

In Eyes 14 6 (42.9) 8 (57.1) 0 ( - ) Glarea 2 2 (100.0) 0 ( - ) 0 ( - ) Halo Visiona 10 10 (100.0) 0 ( - ) 0 ( - ) Lacrimation Increased 5 0 ( - ) 3 (60.0) 2 (40.0) Photophobia 19 7 (36.8) 10 (52.6) 2 (10.5) Photopsia 4 4 (100.0) 0 ( - ) 0 ( - ) Vision Blurreda 10 4 (40.0) 6 (60.0) 0 ( - ) Visual Impairment 6 4 (66.7) 2 (33.3) 0 ( - ) Foreign body sensation at 1 month or laterb Foreign Body Sensation

In Eyes 186 156 (83.9) 28 (15.1) 2 (1.1) Ghost/double images in the operative eyeb Diplopia 86 84 (97.7) 0 ( - ) 2 (2.3) Pain at 1 month or laterb Eye Pain 139 94 (67.6) 40 (28.8) 5 (3.6) E = Number of events n = Number of events in resolution category Percentage is calculated as n/E. a The events glare (n=2, E=4), halos (n=2, E=6), and blurry vision (n=1, E=2) were reported by investigators as AEs based on VSARC responses. Although these events do not meet the protocol specified definition of “Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later”, Alcon considers that they are best accounted for in this table. b Events for these categories were identified through the VSARC questionnaire. Self-reported responses other than none were reported as adverse events.

Study Data


The cumulative rates of non-protocol specified AEs are presented in Table 18. The most frequently reported event was corneal opacity, with a rate of 5.6%. All cases with the exception of 1 eye were reported as resolved. One incidence of corneal opacity/corneal haze at Month 6 was device related. The event was assessed as mild and resolved with treatment by Month 12.

Study Data


Table 19 presents the summary of corneal haze by severity throughout the study. The highest rate of grade 1 or greater corneal haze was at Month 1 (9.7%) and progressively decreased through Month 12 to 1.0%.

Study Data


Contrast sensitivity (the ability to see objects that may not be outlined clearly or that do not stand out from their background) is usually tested under various lighting conditions. Below are the results of contrast sensitivity for subjects in the study:

• At 12 months after PRK:

o 88 out of 311 eyes had significantly better contrast sensitivity in dim light with a glare source

o 70 of 311 eyes had significantly better contrast sensitivity in dim light without a glare source

o 42 of 311 eyes had significantly better contrast sensitivity in bright light with a glare source

o 33 of 311 eyes had significantly better contrast sensitivity in bright light without a glare source

o 19 out of 311 eyes had significantly worse contrast sensitivity in dim light with a glare source

o 20 of 311 eyes had significantly worse contrast sensitivity in dim light without a glare source

o 21 of 311 eyes had significantly worse contrast sensitivity in bright light with a glare source

o 10 of 311 eyes had significantly worse contrast sensitivity in bright light without a glare source

o 204 out of 311 eyes had no significant change in contrast sensitivity in dim light with a glare source

o 221 of 311 eyes had no significant change in contrast sensitivity in dim light without a glare source

o 248 of 311 eyes had had no significant change in contrast sensitivity in bright light with a glare source

o 268 of 311 eyes had had no significant change in contrast sensitivity in bright light without a glare source

Study Data


4.6. Patient Reported Outcomes Results for the Visual Symptoms Associated with Refractive Correction (VSARC) questionnaire are presented in Table 20. At all postoperative visits, most subjects rated their symptoms as none or mild. At Month 6, 4.4% or less of subjects reported moderate or severe symptoms.

Study Data


Study Data


Table 21 presents the outcomes of the Refractive Status and Vision Profile (RSVP) questionnaire. At Month 6, the mean score shows that vision-related quality of life did not worsen following PRK.

Study Data


4.7. Overall Conclusion The primary effectiveness and safety objectives of the C-10-084 study were met. No unanticipated safety risks were revealed. The results of this study establish the effectiveness and safety of the ALLEGRETTO WAVE® EYE-Q excimer laser system for the PRK treatment of myopia up to - 6.0 D sphere and MRSE with or without astigmatism up to - 3.0 D cylinder.

Preparation Of Devices, Instruments And Material


5. PREPARATION OF DEVICES, INSTRUMENTS AND MATERIAL Prepare all material, instruments and devices necessary for surgery. Arrange them conveniently for surgeon and his/her assistant(s) to provide a good workflow during surgery. Mount and test the related disposables. Check all parts and materials for debris and damages. Do not use contaminated or damaged parts and material. For detailed information, refer to the Operator’s Manual, its addendums and additional information. Check environmental conditions in the operating room. Temperature and humidity should match the specifications given in the Operator’s Manual. Solvents, vapors and aerosols must not be present in the operating room.

NOTE

Complications

Additional instruments for management of complications should be prepared.

Treatment Planning And Data Entry


6. TREATMENT PLANNING AND DATA ENTRY Observe all inclusion and exclusion criteria, adverse event, complication, indication, contraindication, warning and precaution information given in this manual for patient selection. The treatment plan and data entry is made and controlled remotely at the laser system. For details regarding data entry and treatment programming please also refer to the Operator’s Manual.

6.1. Treatment Plan And Data Entry Enter all mandatory data and determine / check the parameter treatment carefully. Transfer treatment relevant diagnostic data and entered patient and eye data from the WaveLight GmbH diagnostic device to the ALLEGRETTO WAVE® EYE-Q laser system and the planning station. Verify the transferred examination data and complete any additional entries. Double-check with the patient and assisting personnel to ensure that there are no possible restrictions for the treatment. It is the sole responsibility of the operating surgeon to ensure that all data is accurate and that the treatment can be safely carried out. Save treatment plan with all entries and for later use or retrieval.



CAUTION

Proven Parameter Range

Safety and effectiveness of treatments has not been proven for all available refractions evaluated during the clinical trials that led to the approval of the WaveLight® EX500 laser system. (See chapter 2.1 “Indications For Use” on page 9 for details.)

6.2. Parameters Determining Ablation The treatment is determined automatically by parameters entered before. Parameters determining treatment are “Clinical”, “Vertex Distance (VD)”, “K-Readings”, “Optical Zone” (OZ) and Refractive Aim (planned “Target” refraction). Refraction:

Enter refraction parameters according to patient’s manifest refraction or to your preferred refraction for treatment. Modify refraction according to your own nomogram, if available. Enter target refraction (aim), if not targeted for emmetropia. Correction treatment will be calculated as difference between entered refraction (in section “Diagnostic”) and target refraction (entered in section “Treatment Planning”).

NOTE

Refraction Entry And Vertex Distance

Input of refraction is possible in plus- or minus-cylinder notation. The software converts the entries automatically into a treatment program that will have the least amount of central ablation depth for the intended correction. Enter the Vertex Distance measured during refraction examination. This value will influence treatment, as the correction will be applied on the corneal plane instead of the spectacle plane. It is recommended to measure the vertex distance exactly in patients with deep seated eyes.



CAUTION

Nomogram Use

If a nomogram shall be applied, changes according to the nomogram must be made in Refraction entries. Notes about the change according to nomogram should be made in the patient’s files. Depth of ablation and residual stroma thickness must be calculated and noted before application of any nomogram.

Optical Zone:

The optical zone is displayed and entered in millimeters. Default optical zone is always 6.5 mm. Check the optical zone size with the largest physiologic pupil size measured under mesopic conditions and resulting ablation depth.

6.3. Feasibility Checks Check if all mandatory entries with patient’s data, examination and treatment data are filled correctly. Check resulting correction and ablation depth and match them again with patient’s eye and treatment plan data of the patient’s file. Optical zone and / or refractive parameters may have to be changed, if conflicts are determined in the feasibility checks.



CAUTION

Remaining Thickness

Exceeding the minimum thickness of 250 microns increases the risk for corneal ectasia following treatment.

6.4. Ablation Depth And Remaining Stromal Thickness Check resulting remaining stromal thickness indicated as “Remaining” or “Stroma”. The remaining thickness is calculated as corneal thickness (entry value) minus maximum ablation depth (calculated). The resulting value is displayed in microns (µm). A warning will be displayed as soon as the set minimum value is be violated by actual treatment parameter. The manufacturer’s setting for the alert level is 250 µm.

6.5. Confirm And Save Data The notebook portal software provides a “Summary Window”. This window will display treatment plan information, warnings and messages for final check and confirmation. Double-check all data, messages and warnings. Accept data and possible warnings or consider a different plan for the patient. If a treatment outside the proven parameter range is selected, a warning message will show. Use of such parameter outside the approved range can be confirmed in the summary window. Make sure a valid WaveCard™ is inserted. Press on start to initiate a treatment sequence.


- End -

WaveLight® EX500

ADDENDUM Procedure Manual Photorefractive Keratectomy (PRK) Treatments

Information for professional use

of 55 WaveLight® EX500 1016-3 Addendum Procedure Manual PRK us / Rev.1d / 16-10-24 Item No.: 6675 2015

This Procedure Manual WaveLight® EX500 is valid as from Database Portal Software Version 1.11 (please refer to the User Manual).

Using The Addendum Procedure Manual PRK

WaveLight® EX500 1016-3 Addendum Procedure Manual PRK us / Rev.1d / 16-10-24 Item No.: 6675 2015 Page 3 of 55

USING THE ADDENDUM PROCEDURE MANUAL PRK (Photorefractive Keratectomy Treatments) This manual provides information for the intended clinical use of the PRK option with the WaveLight® EX500 for Photorefractive Keratectomy (PRK) treatments.

This manual provides only information that is specific for PRK. Refer to the User Manual of the laser console, to its addendums, its Procedure Manuals and to the User Manuals of the approved accessories for information regarding these components.

Carefully read and understand this manual and all related documents and instructions before using the WaveLight® EX500 laser system for performing PRK treatments.

Observe all warnings, precautions and contra-indications as described in these documents.

Do not perform adjustments and procedures other than those described in these documents. Failure to do so may result in harm to patient and / or user.

Consult the Table of Contents, Appendices or Indices for specific information. If you have questions that are not addressed in this manual, contact the hotline shown in the User Manual of the laser console.

Am Wolfsmantel 5 91058 Erlangen, Germany

Typographical Conventions

Page 4 of 55 WaveLight® EX500 1016-3 Addendum Procedure Manual PRK us / Rev.1d / 16-10-24 Item No.: 6675 2015

WARNING

A “Warning” alerts the user to potential serious outcomes to the patient or user in case of non-observance of this warning.

CAUTION

“Precautions” alert the reader to exercise special care necessary for the safe and effective use of the device.

TYPOGRAPHICAL CONVENTIONS The following conventions and symbols are used in this manual for Warnings, Precautions and Notes:

NOTE

“Notes” provide helpful or supplementary information to the user.

Notice To Users


CAUTION

RESTRICTED DEVICE

U.S. Federal Law restricts this device to sale, distribution, and use by or on the order of a physician or other licensed practitioner. U.S. Federal Law restricts this device to practitioners who have been trained in its calibration and operation and who have experience in the surgical management and treatment of refractive errors.

CAUTION

Other Manuals

This addendum is only valid in conjunction with related manuals. Read this Addendum Procedure Manual and all related manuals of the laser system and its approved accessories carefully before starting to use the WaveLight® EX500 laser system. The system user alone is responsible for having sufficient medical knowledge for carrying out all surgical procedures.

NOTICE TO USERS There are no rightful claims to system upgrades in the event of the introduction of product improvements based on new technological developments.

Notice To Users


This documentation is copyrighted with all rights reserved. Under copyright laws this documentation may not be reproduced or transmitted in whole or in part in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from WaveLight GmbH. Permitted copies must carry the same proprietary and copyright notices as were affixed to the original. Under the law, copying includes also translation into other languages.

Please note that while every effort has been made to ensure that the data given in this documentation is accurate, the information, figures, illustration, tables, specifications and schematics contained herein are subject to change without notice.

All images are representative. The numbers shown in the images are just examples and may not represent typical values. Some sections of this documentation may not apply for all devices. Such sections will be marked accordingly. Other documentations may apply as well for use of the device described herein.

WaveLight® is a registered trademark of WaveLight GmbH. WaveLight® FS200 and WaveLight® EX500 are registered trademarks of WaveLight GmbH. WaveLight® Refractive Suite is a registered trademark of WaveLight GmbH. ALLEGRETTO WAVE® EYE-Q is a registered trademark of WaveLight GmbH. WaveNet™ is a registered trademark of WaveLight GmbH. WaveNet™ Planning Software is a registered trademark of WaveLight GmbH. WaveNet™ Server is a registered trademark of WaveLight GmbH. WaveLight® Analyzer II is a registered trademark of WaveLight GmbH. WaveLight® Oculyzer II is a registered trademark of WaveLight GmbH. WaveLight® OB820 is a registered trademark of WaveLight GmbH. Wavefront Optimized™ is a registered trademark of WaveLight GmbH. Custom Q® is a registered trademark of WaveLight GmbH. PerfectPulse Technology® is a registered trademark of WaveLight GmbH. Right.From the Start.® is a registered trademark of WaveLight GmbH. Accutane® is a registered trademark of Hoffmann-La Roche Inc. Cordarone® is a registered trademark of Wyeth Inc. Imitrex® is a registered trademark of GlaxoSmithKline Inc. Zeiss and OPMI are registered trademarks of Carl Zeiss. Microsoft, Windows™ is a registered trademark of Microsoft Corporation. 7-Zip is under the GNU LGPL license, http://7-zip.org/download.html (please refer to the User Manual) © Copyright by WaveLight GmbH, Germany All Rights reserved

Contents


CONTENTS Page

1. DEVICE DESCRIPTION ..................................................................................... 9

2. INDICATIONS, CONTRAINDICATIONS, PRECAUTIONS, ............................. 11

2.1. Indications For Use ............................................................................ 11

2.2. Contraindications ................................................................................ 11

2.3. Precautions ........................................................................................ 12

2.4. Warnings ............................................................................................ 13

2.5. Patient Selection ................................................................................ 14

3. PROCEDURE ................................................................................................... 15

3.1. Procedure Steps ................................................................................. 15

3.1.1. Patients Preparation And Surgery ...................................................... 16

3.2. Treatment Interruption ........................................................................ 17

3.3. Ablation Details .................................................................................. 18

3.4. Typical Treatment Profiles .................................................................. 19

3.5. Optical Zones ..................................................................................... 19

3.6. Post Procedure ................................................................................... 20

4. PRK STUDY DATA .......................................................................................... 21

4.1. Study Design ...................................................................................... 21

4.2. Study Objective .................................................................................. 21

4.3. Data Analysis ..................................................................................... 22

Contents


Page

4.4. Effectiveness Results ......................................................................... 27

4.5. Safety Results .................................................................................... 34

4.6. Patient Reported Outcomes ............................................................... 44

4.7. Overall Conclusion ............................................................................. 47

5. PREPARATION OF DEVICES, INSTRUMENTS AND MATERIAL ................. 48

6. TREATMENT PLANNING AND DATA ENTRY ................................................ 49

6.1. Treatment Plan And Data Entry .......................................................... 49

6.2. Parameters Determining Ablation ....................................................... 50

6.3. Feasibility Checks............................................................................... 52

6.3.1. Ablation Depth And Remaining Stromal Thickness ............................ 52

6.4. Confirm And Save Data ...................................................................... 53

7. INDEX ............................................................................................................... 54

Device Description


1. DEVICE DESCRIPTION Intended Use:

The refractive laser WaveLight® EX500 is a stationary scanning-spot excimer laser system used in refractive surgery for the treatment of myopia, myopic astigmatism, hyperopia, hyperopic astigmatism, mixed astigmatism, including customized refractive surgery based on data delivered by WaveLight GmbH diagnostic devices. Please see “Indications For Use” in the Procedure Manual. The WaveLight® EX500 laser system is also used for photorefractive treatments including Photorefractive Keratectomy (PRK) as described in chapter 2.1 “Indications For Use” on page 11. The excimer laser creates a radiation of 193 nm wavelength. This radiation is able to ablate corneal tissue in very thin layers without damage or thermal alteration of collateral tissue. The ablation effect is threshold dependent - the energy per irradiated area, known as Fluence, has to be above a certain threshold to ablate corneal tissue. Below the threshold the radiation will cause heating instead of ablation. The laser radiation is used to change the front shape of the corneal lens by ablating tissue. This sculpting has to be done with very high precision in order to achieve a new corneal lens shape with the desired smoothness of surface and precision of optical power. Every single laser pulse (spot) has to meet very high requirements regarding precision of ablated depth, volume and spot position. The WaveLight® EX500 laser system consists of a combination of features including several internal energy control mechanisms and external test procedures to provide the right energy and fluence per laser pulse. The fast eyetracker for determining eye position and a precise scanner motor for positioning the laser spot enable precise placement of every laser spot even when the eye is moving or having saccades. In addition, the eyetracker offers an automatic centration of the ablation to avoid unintended decentration of the correction zone. The Gaussian shaped energy distribution within the laser beam and a small ablation spot of approximately 1 mm assure the desired contour precision and high surface smoothness of the newly shaped corneal curvature. The ablation profiles that are used in the WaveLight® EX500 are “Wavefront Optimized” meaning that the initial profiles, which can be calculated mathematically, were refined by empirical research with a wavefront aberrometer. Due to the small spot diameter used in the WaveLight® EX500, the excimer laser beam source is compact with low laser gas volume and minimal laser gas consumption.

Device Description


The WaveLight® EX500 excimer laser system is used to treat refractive vision problems, such as nearsightedness with or without astigmatism. This excimer laser system is approved in the United States to perform LASIK (laser-assisted in situ keratomileusis) treatment. With this procedure, a thin flap is created in the cornea, the laser reshapes the inner layers of the cornea after the flap is lifted, and then the flap is repositioned. With PRK, there is no flap created. The corneal epithelium is removed with techniques including manual blade scrape, amoils brush and dilute alcohol assisted. Then the laser is applied to reshape the cornea. This laser, which delivers a cool pulsing beam of ultraviolet light, is used on the surface of the cornea and not underneath a flap made in the cornea, as in LASIK.

Indications, Contraindications, Precautions,


2. INDICATIONS, CONTRAINDICATIONS, PRECAUTIONS, WARNINGS AND PATIENT SELECTION

2.1. Indications For Use The WaveLight® EX500 laser system is indicated for use in Photorefractive Keratectomy (PRK) treatments for:

• the reduction or elimination of up to - 6.0 diopters (D) of spherical equivalent myopia or myopia with astigmatism, with up to - 6.0 D of spherical component and up to - 3.0 D of astigmatic component at the spectacle plane,

• patients who are 18 years of age or older and

• patients with documentation of a stable manifest refraction defined as ≤ 0.5 D preoperative spherical equivalent shift over one year prior to surgery.

2.2. Contraindications PRK treatments using the WaveLight® EX500 laser are contraindicated if any of the following conditions exist. Potential contraindications are not limited to those included in this list:

• progressive myopia with or without astigmatism, acute or recurrent ocular disease, previous corneal or intraocular surgery, or trauma in the ablation zone,

• patients with a weakened immune system, diagnosed collagen vascular, atopic syndrome, autoimmune or immunodeficiency disease,

• patients with degeneration of structures of the cornea, diagnosed keratoconus or any clinical pictures suggestive to keratoconus,

• patients with uncontrolled glaucoma. It is unknown whether PRK is safe and effective for such patients,

• patients with severe dry eye,

• patients with uncontrolled diabetes,

• patients with a thin cornea and which is not thick enough to undergo the necessary ablation for the PRK procedure,

• patients with eyes that have a calculated residual stromal bed thickness that is less than 250 microns,

• patients with recurrent corneal erosion. This condition can lead to serious corneal problems during and after PRK.

• Eyes with unstable visual acuity by manifest refraction (change of more than 0.5 diopter in myopia or astigmatism) over the prior 12 months preceding surgery.

• Herpes (herpes simplex or herpes zoster) eye infection within the past year or corneal damage from prior herpes eye infections.



2.3. Precautions Safety and effectiveness of the WaveLight® EX500 for PRK treatments has not been established for patients with: • with acute or recurrent ocular disease, previous corneal or intraocular surgery, or

trauma in the ablation zone, • corneal abnormalities including, but not limited to, scars, irregular astigmatism and

corneal warpage,

• history of glaucoma or ocular hypertension of > 23 mmHg, • taking the medication sumatriptan succinate (Imitrex®1), • taking the medication amiodarone hydrochloride (Cordarone®2), • under 18 years of age,

• corneal, lens and/or vitreous opacities including, but not limited to cataract, • iris problems including, but not limited to, coloboma and previous iris surgery

compromising proper eye tracking,

• treatments with an optical zone notwithstanding 6.5 millimeters in diameter, • treatment targets different from emmetropia (plano) in which the calculated defocus

(spherical term) and the astigmatism (cylinder term) has been adjusted, additionally, physician adjustment of calculated defocus may negate the potential benefits of the PRK procedure. You should discuss with your patient the potential risks and benefits associated with treatment targets different from emmetropia,

• myopia with or without astigmatism that is not within the FDA-approved treatment range of - 6.0 D MRSE, up to - 6.0 D sphere, or up to - 3.0 D cylinder,

• large pupils,

• with severe allergies or eye rubbing condition • pupil sizes should be evaluated under mesopic illumination conditions. Effects of

treatment on vision under poor illumination cannot be predicted prior to surgery. Some patients may find it more difficult to see such in conditions as very dim light, rain, fog, snow and glare from bright lights. This has been shown to occur more frequently in the presence of residual refractive error and perhaps in patients with pupil sizes larger than the optical zone size.

• undiagnosed dry eyes, • any other medical condition that might be expected to make the patient an

unsuitable candidate for PRK treatment, • mixed astigmatism. It is unknown whether PRK is safe and effective for such patients. • PRK will also cause difficulties with future health:

o future IOP measurements o future cataract surgery

• pregnant or nursing women 1 Imitrex® is a registered trademark GlaxoSmithKline Inc. 2 Cordarone® is a registered trademark of Wyeth Inc.



If there is an infection or problem with healing after the surgery, it is more likely that both eyes will be affected if both eyes are treated at the same session. If only one eye is treated, the difference in vision between the treated eye and the one without treatment might make vision difficult. In such a case, the patient might not have functional vision unless the second eye is treated with PRK or by wearing glasses or contact lenses that compensate for the difference. The refraction is determined in the spectacle plane, but treated in the corneal plane. In order to determine the right treatment program to achieve the right correction, assessment of the vertex distance during refraction test is recommended. Preoperative evaluation for dry eyes should be performed. Patients should be advised of the potential for dry eyes post PRK surgery.

2.4. Warnings Any PRK treatment with the WaveLight® EX500 is not recommended in patients who have:

• controlled autoimmune or connective tissue disease,

• significant dry eye that is unresponsive to treatment,

• uncontrolled or untreated eye allergies,

• controlled glaucoma, ocular hypertension, or being followed for possible glaucoma (glaucoma suspect),

• taking the medication isotretinoin (Accutane®3).

• patients with controlled diabetes

• Patients with weakened immune system

• Patients with history of eye injury and eye pain

• Patients with history of strabismus

• Patients with decreased vision in one eye A complete examination, including, but not limited to cycloplegic evaluation must be performed. Direct and indirect ophthalmoscopy through a dilated pupil is essential. Evaluation of the optic nerve and measurement of IOP are necessary. If there are any concerns regarding the appearance of the optic nerve, a threshold test of the visual field should be performed. Baseline evaluation of patients with myopia desiring refractive surgery should be performed within 30 days prior to PRK surgery.

3 Accutane® is a registered trademark of Hoffmann-La Roche Inc.



2.5. Patient Selection In addition to contraindications, precautions and warnings the following should be considered and discussed with your patient in order to find good candidates for PRK and to get sufficient information for the treatment plan:

• A complete baseline exam including, but not limited to, cycloplegic refraction within 60 days prior to surgery is necessary.

• A slit lamp exam has to be performed. The status of the lens has to be evaluated to ensure that neither nuclear sclerosis nor other lens opacities are present. These opacities may adversely affect final visual result.

• Dilated fundus exam by indirect ophthalmoscopy has to be performed, as retinal pathology is more likely in patients with myopia.

• Optical nerve and intraocular pressure have to be examined as glaucoma is more common in myopic than in emmetropic subjects. If elevated pressure or signs of glaucomatous damage are found, topical steroids should be used only under careful medical supervision or the patient should not be treated.

• In order to exclude corneal abnormalities careful videokeratography (topography) is essential.

• Contact lens wearers must discontinue wearing hard or gas permeable lenses for at least 3 weeks and soft lenses for at least 1 week prior to preoperative evaluation.

• Contact lens wearers must also discontinue wearing hard or gas permeable lenses for at least 3 weeks and soft lenses for at least 1 week prior to surgery.

• The patient must be able to lie flat in a supine position.

• Topical or local anesthesia must be tolerated.

• The patient must be able to fixate steadily.

• The patient must be able to understand and give the informed consent and sign the informed consent form.

• All alternatives to the PRK procedure for correcting myopia with or without astigmatism by spectacles, contact lenses and other surgical procedures such as LASIK, radial keratotomy, automated lamellar keratoplasty or clear lens exchange should be clearly communicated and understood by the patient.

• Additionally patients should be instructed not to wear makeup at the day of surgery. Patients must not use perfumes, aftershave, Eau de Cologne or other substances applied to the skin containing alcohol at that day.

• Patients with heart pacemakers may not be treated.

Procedure


3. PROCEDURE

3.1. Procedure Steps The determined patient and eye data have to match with the patient presenting and with the eye prepared for surgery. Make sure that treatment parameters are precisely transferred from the files to the laser system. A double check with the patient and assisting personnel is recommended. It is the sole responsibility of the operating surgeon to ensure that all data is accurate.

Instruct patients not to wear makeup as this poses risk for contamination of the stromal interface. Patients must not use perfumes, after shave, eau de cologne or other substances applied to the skin containing alcohol.

Aromatic substances and solvents including, but not limited to alcohol, fresh glue and paint should not be noticeable at the laser aperture. Vapors of all such substances absorb energy of the laser pulses and therefore may cause undercorrections.

Strong disturbances of the air between the laser aperture and the patient’s head during laser ablation must be avoided. Switch off any ventilation device causing a noticeable airflow during ablation, with exception of the plume evacuator of the laser system. Instruct personnel not to move around and keep doors and windows closed during ablation. Uncontrolled airflow may have an effect on the quality of the ablation.

Potentially noisy devices such as telephones that may cause a sudden sound during the procedure should be switched off. Sudden noise may distract surgeon and / or patient.

The use of mobile telephones is restricted in the treatment area.

The corneal epithelium should be removed, with a total epithelium removal diameter of approximately 9.0 mm. Methods of removal include manual blade scrape, Amoils brush, or dilute alcohol-assisted.

Medications likely to dilate or constrict the pupil should be administered with careful supervision during the last 6 hours prior to surgery as the eyetracker will not be able to track pupils of less than 1.5 mm and more than 8.0 mm diameter. Furthermore, such medication might influence the physiological center of the pupil and compromise centration of the eye tracking system.

Check that the patient is able to see the green blinking fixation light and to distinguish it from other light sources around the laser aperture (see Procedure Manual, chapter “Patient’s Views”).

Perform an Energy Check according to the User Manual prior to treating a new patient. The cross-line projector can be used to align the patient’s head position, but must be switched off during the course of the ablation process.

Repeat the test if more than 30 minutes have elapsed before the treatment is begun.

Head alignment in order to apply cylinder treatment in the right axis is essential.

The ablation treatment is triggered by pressing the LASER foot pedal. It can be interrupted at any time by leaving the pedal. The laser will stop automatically when the treatment process is finished.

Procedure


3.1.1. Patients Preparation And Surgery Position the patient’s head under the microscope. Adjust the focus with the distance diodes. Switch-on the cross line projector pressing the “Cross Line Projector Key” (if not activated by default) Adjust the brightness of the cross-line to your personal needs using the “Cross Line Brightness Knob”. Check patient’s head position using the cross line projector (see picture below) and deactivate the cross line projector thereafter. Figure 1: Crossline Overlay - Patient’s Head Move eye to be treated into a roughly focused and centered position. Instruct patient about fixation light: It can be distinguished from all other light-sources of the WaveLight EX500 by its blinking characteristic and green color. Note that the patient can see the Fixation Light best from an almost centered position. As long as the patient fixates well, the observer (at the microscope) will see a small green blinking light projection (Purkinje image) on the cornea (in the center of the op-field illumination). The fixation light can temporarily be reduced or switched off completely to assist the patient in recognizing the fixation light. Drape operational field or eye and drape lids and lashes according to your needs. Apply topical anesthetic before or after inserting the lid speculum to the surgeon’s discretion. Insert lid speculum.

Procedure


3.2. Treatment Interruption If laser ablation is interrupted, the parameters remain in the system and the system will proceed with the ablation pattern exactly at that point, at which the treatment was interrupted. The progress of the ablation procedure is indicated on the monitor screen of the laser console. If for any reason a treatment has to be terminated before ablation was completed, the residual time of treatment accomplished has to be recorded and kept in the patient files. The system will automatically store the progress of the surgery, if a treatment is terminated for any reason. The system allows loading the previously aborted treatment. The treatment will continue from the point of termination. Please also refer to the User Manual. Figure 1: Treatment Window - Progress Indicators

Procedure


3.3. Ablation Details During ablation spherical and astigmatic error are treated separately. The spherical portion of the refractive treatment is applied first; the astigmatic portion follows immediately without interruption. Please note that the treatment progress indicated by the software is neither related to the amount of ablated diopters, nor to a certain ablation zone. Figure 2: Relation Of Optical Zone To Ablation Depth; Myopic Myopic astigmatism treatments flatten the axis of the (positive) cylinder. Keep the stromal surface dry and clean during ablation. Prevent liquid from running towards the ablation zone. Liquid and debris will shield the stromal surface against ablation. Irregular ablations will most likely result, if liquid reaches the optical zone area. Irregular ablations may lead to deviation of the best possible clinical results. Do not move instruments across or in the area of the intended optical zone during laser ablation. The instrument may shield the stroma partially against ablation. Resulting irregular ablations may lead to a deviation of the best possible clinical result. Optical zones are always circular. The ablation zone shape depends on treatment type. Optical and ablation zone diameters are indicated on the monitor screen. Avoid shadowing of any of the three infra-red illumination spots during registration and ablation, as this might cause interference to the detection of the pupil and centration.

Procedure


3.4. Typical Treatment Profiles The following figures show typical ablation depth profiles for myopic spherical and cylindrical treatments (the higher the profile or the “hotter” the color, the deeper the ablation). Figure 3: Myopic Ablation Depth Profiles For Sphere (Left), Cylinder (Middle) And Spherocylinder (Right)

3.5. Optical Zones The optical zone is the area where the intended correction treatment is applied. Optical zones treatments are circular for all types of treatments. They are surrounded by a blend zone, called transition zone. Both add up to the ablation zone. The ablation zone determines the area hit by laser pulses. The shape of transition and ablation zone varies due to the type of treatment. Ablation zones of myopic spheres are circular. Ablation zones of myopic cylinders are elliptical. Figure 4: Optical And Ablation Zone Myopic Treatments

Procedure


3.6. Post Procedure After ablation, the operative eye should be irrigated with a balanced salt solution (BSS). A bandage contact lens can be used on the treated eye until re-epithelialization has occurred. Antibiotics and steroid anti-inflammatory drops may be used after treatment as needed. Ocular or oral pain medications may be prescribed for early postoperative pain management. Postoperative follow-up should occur, at minimum, the first day after surgery and very day until the re-epithelialization is complete.

PRK Study Data


4. PRK STUDY DATA

4.1. Study Design This study was a prospective, multi-center, single group, safety and effectiveness study conducted at eight (8) clinical sites in the US. A total of 320 eyes with myopia, with or without astigmatism, had photorefractive keratectomy (PRK) with the ALLEGRETTO WAVE EYE-Q excimer laser system. Subjects who agreed to participate in the clinical study provided informed consent and underwent the required screening procedures to determine study eligibility. Subjects in whom at least one eye had a preoperative refractive error within the specified range (Sphere and MRSE up to - 6.0 D and cylinder up to -3.0 D) and met all study eligibility criteria had PRK. Corneal topography, pachymetry, keratometry, pupillometry, aberrometry, manifest refraction and measurements of uncorrected visual acuity (UCVA) were obtained at baseline and at scheduled times after PRK to evaluate study eligibility and/or effectiveness of the treatment. Safety monitoring throughout the study included adverse event reporting at scheduled and unscheduled visits, contrast sensitivity, clinically significant findings from dilated fundus and slit lamp examinations and measurements of best spectacle corrected visual acuity (BSCVA) at baseline and at scheduled times after PRK. Subjects completed questionnaires to evaluate subjective visual complaints prior to and after PRK. Treatment planning was done with Wavefront Optimized profiles. The laser software used the nomogram adjusted manifest refraction data to determine the treatment plan for PRK. All eyes were targeted for emmetropia.

4.2. Study Objective The purpose of this study was to evaluate the safety and effectiveness of PRK for myopia with or without astigmatism using the ALLEGRETTO WAVE EYE-Q excimer laser system.

PRK Study Data


4.3. Data Analysis The intent-to-treat (ITT) data set was the primary dataset for the effectiveness analyses. All subjects who underwent surgery were included in the ITT data set. The safety dataset was the dataset used for all safety analyses. All subjects enrolled in the study who underwent a surgical procedure (any instrument touches the eye in the operating room) were included in the safety dataset. Safety and effectiveness cohorts may differ in number depending on the availability of data at each time point of analysis. Subject disposition is presented in Table 1 for the 176 subjects that enrolled (signed informed consent) in the study. Fifteen subjects did not meet inclusion and exclusion criteria and were considered screen failures. A total of 161 subjects were treated. For 2 subjects, only 1 eye was treated (the fellow eye did not qualify). Nine subjects discontinued from the study.

Table 1: Subject Disposition (All Enrolled)

n (%) Enrolled 176 Screen Failures 15 Treateda 161 (100.0) Completed Study 152 (94.4) Discontinued 9 (5.6) Lost to Follow-up 7 (4.3) Unable to Make Future Office Visits 2 (1.2) n = Number of subjects in category a Subjects 1001 and 1002 had only one eye treated.

PRK Study Data


Demographic characteristics of the subjects enrolled in the study are summarized in Table 2. The age of the subjects ranged from 18 to 64 years, with a mean age of 31.5 years at the time of screening. The subject population consisted of a similar percentage of male (44.7%) and female (55.3%) subjects and was predominantly white (78.3%) of non-Hispanic or Latino ethnicity (88.8%).

PRK Study Data


Preoperative baseline characteristics included manifest refraction sphere, manifest refraction cylinder, MRSE (manifest refraction spherical equivalent), UCVA (uncorrected visual acuity) in logMAR, and BSCVA (best spectacle corrected visual acuity) in logMAR. Table 3 presents the summary statistics for the baseline characteristics by eye.

Table 3: Baseline Characteristics by Eye, (Intent-to-Treat)

Baseline Characteristic Statistic Results Manifest Sphere n 320 Mean -2.957 SD 1.4843 Median -2.75 (Min, Max) (-6.00, -0.25) 95% CI (-3.120, -2.794)

Manifest Cylinder n 320 Mean -0.788 SD 0.8191 Median -0.50 (Min, Max) (-3.00, 0.00) 95% CI (-0.878, -0.697)

MRSE n 320 Mean -3.351 SD 1.4191 Median -3.25 (Min, Max) (-6.00, -0.75) 95% CI (-3.507, -3.195)

UCVA n 320 Mean 0.870 SD 0.2656 Median 0.92 (Min, Max) (0.28, 1.40) 95% CI (0.841, 0.900)

BSCVA n 320 Mean -0.085 SD 0.0741 Median -0.10 (Min, Max) (-0.28, 0.12) 95% CI (-0.093, -0.076)

n = Number of eyes in ITT analysis set with data SD = Standard deviation, Min = Minimum, Max = Maximum CI = Confidence Interval MRSE = Manifest refraction spherical equivalent UCVA = Uncorrected visual acuity BSCVA = Best-spectacle corrected visual acuity

PRK Study Data


The preoperative bin distribution based on the preoperative manifest refraction is summarized in Table 4, with stratification based on sphere and cylinder. An adequate number of eyes were treated in each sphere and cylinder bin. Accountability by eye is summarized in Table 5. There was good accountability in this study with a high percentage of eyes that were available for analysis, ranging from 97.2% to 100%, with the lowest percentage at Month 12.

PRK Study Data


Table 6 presents the MRSE and manifest refractive cylinder results. The time point of refractive stability was established at Month 6 (Visit 8) because the following criteria were met for the Month 3 to Month 6 interval:

• 99.7% and 100% of eyes had a change of MRSE and manifest refractive cylinder of ≤ 1.0 D, respectively

• The mean rate of change per year was -0.019 D and 0.038 D for MRSE and manifest refractive cylinder respectively

• The 95% confidence interval for the mean rate of change included zero

• The mean rate of change decreased towards zero over time, although there was clinically non-significant increase or decrease in mean change in MRSE and manifest refractive cylinder between consecutive intervals over time

• The refractive stability criteria were confirmed for the Month 6 to Month 9 interval

PRK Study Data


4.4. Effectiveness Results A total of 299 eyes with pre-operative best spectacle-corrected visual acuity (BSCVA) of 20/20 or better participated in the study. The primary effectiveness objectives were:

• To demonstrate that, at refractive stability, the percentage of eyes that achieve uncorrected visual acuity (UCVA) of 20/40 or better (in eyes with best spectacle corrected visual acuity (BSCVA) 20/20 or better preoperatively) would be equal to or greater than 85%

• To demonstrate that 95% of eyes would have a change of ≤ 1.0 diopter (D) in manifest refraction spherical equivalent (MRSE) and manifest refractive cylinder between 2 refractions, performed at 1 and 3 months postoperatively, or over a minimum 3 month period thereafter


• To demonstrate that, at refractive stability postoperatively, the percentage of eyes achieving manifest refractive cylinder within ± 1.0 D of zero would be equal to or greater than 75%


• To demonstrate that, at refractive stability, the percentage of eyes achieving manifest refractive cylinder within ± 0.5 D of zero would be equal to or greater than 50%

The proportion of eyes that met the visual and refractive outcome criteria is summarized in Table 7. These results are that at Month 6:

• 100% of eyes with preoperative BSCVA of 20/20 or better achieved UCVA of 20/40 or better



• 99.0% of eyes achieved manifest refractive cylinder within ± 1.0 D of zero

• 92.7% of eyes achieved MRSE within ± 0.5 D of zero The results after Month 6 are consistent or slightly better than the results at Month 6.

PRK Study Data


As shown in Table 8, a change of ≤ 1.0 D in MRSE and manifest refractive cylinder between 2 refractions performed at 1 and 3 months postoperatively or over a minimum 3-month period thereafter was observed for 95.6% of eyes. Furthermore, within the interval that included the time point of refractive stability (between Month 6 to Month 9 visits), a change of ≤ 1.0 D in MRSE and manifest refractive cylinder was observed in 99.7% of eyes.

Table 7: Proportion of Eyes Meeting Visual and Refractive Outcome Criteria, (Intent-to-Treat)

Visit Parameter n / N (%) 95% CI† Visit 5 - Week 1 UCVA 20/40 or better (BSCVA 20/20 or better pre-op) 270 / 299 (90.3) (86.4, 93.4) MRSE within ± 1.00 D of emmetropia 307 / 320 (95.9) (93.2, 97.8) MRSE within ± 0.50 D of emmetropia 255 / 320 (79.7) (74.9, 84.0) Manifest refractive cylinder within ± 1.00 D of plano 296 / 320 (92.5) (89.0, 95.1) Manifest refractive cylinder within ± 0.50 D of plano 250 / 320 (78.1) (73.2, 82.5)







PRK Study Data


PRK Study Data


Table 9 presents the results for eyes that achieved UCVA of 20/20 or better and 20/40 or better. At Month 6, 93.0% of eyes had UCVA of 20/20 or better and 100% of eyes had UCVA of 20/40 or better. Similar results were seen after Month 6.

PRK Study Data


The summary of the non-vector results of MRSE and visual acuity at Month 6 are presented in Table 10. All eyes had MRSE within ± 2.0 D of zero. The percentage of eyes undercorrected by greater than 1.0 D MRSE was low at 0.3%; no eyes were overcorrected by more than 1.0 D MRSE. The majority of eyes (68.5%) had UCVA better than or equal to their preoperative BSCVA. Finally, no eyes showed a decrease from baseline in BSCVA of 2 lines or greater. Table 10: Non-Vector Analyses by Eye at Refractive Stability Time Point (Month 6),

(Intent-to-Treat)

Parameter n / N (%) 95% CI† MRSE ± 2.00 D of emmetropia 314 / 314 (100.0) (98.8, 100.0) Overcorrected by > 1.00 D MRSE 0 / 314 (0.0) (0.0, 1.2) Overcorrected by > 2.00 D MRSE 0 / 314 (0.0) (0.0, 1.2) Undercorrected by > 1.00 D MRSE 1 / 314 (0.3) (0.0, 1.8) Undercorrected by > 2.00 D MRSE 0 / 314 (0.0) (0.0, 1.2) UCVA equal to or better than preoperative BSCVA Difference in postoperative and preoperative BSCVA

215 / 314 (68.5) (63.0, 73.6)

< -2 lines 3 / 314 (1.0) (0.2, 2.8) -2 lines 7 / 314 (2.2) (0.9, 4.5) -1 line 83 / 314 (26.4) (21.6, 31.7) 0 lines 218 / 314 (69.4) (64.0, 74.5) 1 line 3 / 314 (1.0) (0.2, 2.8) 2 lines 0 / 314 (0.0) (0.0, 1.2) > 2 lines 0 / 314 (0.0) (0.0, 1.2) N = Number of eyes in ITT analysis set with data at visit n = Number of eyes in category † 95% confidence interval from Binomial distribution

Table 11 presents the results for the accuracy of cylinder to target in eyes that had preoperative astigmatism. At Month 6, 98.7 % of eyes were within ± 1.0 D of cylinder target (zero), and 91.1% were within ± 0.5 D of cylinder target. Table 11: Accuracy of Cylinder to Target by Eye, (Intent-to-Treat)

Cylinder Visit 1

Screening Visit 6

Month 1 Visit 7

Month 3 Visit 8

Month 6 Visit 9

Month 9 Visit 10

Month 12 No. Eyes (N) 230 230 227 224 224 223 Mean ± SD -1.096

± 0.77 -0.393 ± 0.43

-0.227 ± 0.30

-0.209 ± 0.29

-0.185 ± 0.28

-0.179 ± 0.29

Attempted change ± SD

1.096 ± 0.77

Achieved change ± SD

0.702 ± 0.90

0.866 ± 0.78

0.886 ± 0.78

0.910 ± 0.77

0.904 ± 0.76


69.1 90.3 91.1 94.2 94.2


93.0 98.7 98.7 98.7 98.7

N = Number of eyes with preoperative cylindrical component with data at visit SD = Standard deviation

PRK Study Data


Results of the vector analyses at Month 6 are presented in Table 12. The mean error vector (EV), defined as the vector difference between the intended refractive correction and the surgically induced refractive correction (IRC - SIRC), was low (< 0.2), indicating a low postoperative astigmatic correction vector. The mean correction ratio (CR), which is the ratio of the achieved correction magnitude to the required correction magnitude, was close to the ideal of 1 in each preoperative cylinder category. Error ratio (ER), defined as the proportion of the intended correction that was not successfully treated, was small in each preoperative cylindrical category, and showed a progressive decrease in mean with increasing preoperative cylinder.

Table 12: Vector Analysis Summary by Eye at Stability Time Point (Month 6), (Intent-to-Treat)

PRK Study Data


Table 13: Summary of Select Primary Effectiveness Endpoints by Eye at Refractive

Stability Time Point (Month 6) by Cylinder Bin (Intent-to-Treat)

Table 14: Summary of Select Primary Safety Endpoints by Eye at Refractive Stability Time Point (Month 6) by Cylinder Bin

(Intent-to-Treat)

NOTE

Because the ALLEGRETTO WAVE EYE-Q device does not have a cyclorotation correction feature, cyclorotation correction was not used in the pivotal clinical trial. The clinical trial was not designed to specifically investigate the potential clinical impact of the absence of cyclorotation correction.

PRK Study Data


4.5. Safety Results The primary safety objectives of this study were:

• To demonstrate that the observed rate of each type of ocular serious adverse event (SAE) would be no more than 1%

• To demonstrate that the percentage of eyes with BSCVA decrease of ≥ 2 lines from baseline would be less than 5% at refractive stability

• To demonstrate that the percentage of eyes with a BSCVA worse than 20/40 (for eyes with BSCVA of 20/20 or better preoperatively) would be less than 1% at refractive stability

• To demonstrate that the percentage of eyes with > 2.00 D of induced manifest refraction cylinder magnitude as compared to baseline would be less than 5% at refractive stability

The following ocular serious adverse events were defined in the protocol and reported:

• Corneal infiltrate or ulcer

• Any persistent corneal epithelial defect at 1 month or later

• Corneal edema at 1 month or later

• IOP with increase of > 10 mmHg above baseline on 2 consecutive examinations or an

• IOP greater than 30 mmHg on 2 consecutive examinations

• Haze beyond 6 months with loss of 2 lines or greater (≥ 10 letters ETDRS) of BSCVA

• Decrease in BSCVA of greater than or equal to 2 lines (≥ 10 letters ETDRS) not due to irregular astigmatism as shown by rigid contact lens refraction at 3 months or later

• Retinal detachment

• Retinal vascular accidents

• Any other vision-threatening event

• Ocular penetration

PRK Study Data


The cumulative rate of SAEs is presented in Table 15. The observed rate of any SAE event type was less than 1%, achieving one of the co-primary safety objectives. The corneal infiltrate events occurred at 1 day after PRK and resolved with medications. The corneal edema event occurred at approximately 5 months after PRK and resolved without treatment. All events were assessed as being unrelated to the device and related to the PRK procedure.

Table 15: Cumulative Incidence of Serious Ocular Adverse Events by Eye (Intent-to-Treat)

PRK Study Data


Results of other co-primary safety outcomes are presented in Table 16. All co-primary safety results achieved the target rates at Month 6. No eyes had BSCVA decrease of ≥ 2 lines from baseline, or BSCVA worse than 20/40 (in eyes with BSCVA of 20/20 or better preoperatively), or > 2.00 D of induced manifest refraction cylinder compared to baseline. Similar results were seen after Month 6.

Table 16: Best Spectacle Corrected Visual Acuity and Manifest Cylinder by Eye (Intent-to-Treat)

PRK Study Data


The following ocular non-serious adverse events were defined in the protocol and reported:

• Corneal edema between 1 week and 1 month after the procedure

• Peripheral corneal epithelial defect at 1 month or later

• Recurrent corneal erosion at 1 month or later

• Foreign body sensation at 1 month or later

• Pain at 1 month or later

• Ghost/double images in the operative eye

• Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later which the investigator has determined is not easily resolved when the subject is wearing correction or has some simple explanation unrelated to the treatment. The investigator should use his medical judgment to determine if one or both eyes are experiencing the symptom marked moderate or severe (e.g. Examine slit lamp findings) and document this on the adverse event case report form. Justification should be provided on the comments case report form if the symptom is not considered an AE

• Clinical signs consistent with marked to severe dry eye at 6 months or later

• Any symptoms of dry eye that significantly affect comfort or activities of daily living

• (as reported to the investigator) at 6 months or later

• Any symptoms of glare or haloes that significantly affect comfort or activities of daily

• living (as reported to the investigator) at 6 months or later Table 17 presents the rates of non-serious protocol-specified AEs for only those participants with a “moderate” or “severe” VSARC questionnaire result (foreign body sensation, ghosting/double images, pain). As shown in tables 18 and 19, these adverse events were mostly mild in severity and the majority resolved by 12 months postoperative. Within the AE category of “Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later”, 4.1% of eyes had pain, 4.4% of eyes had foreign body sensation, and there were no reports of ghost or double images. The overall rate of “Any symptom marked moderate or severe on the VSARC questionnaire at Month 6 or later” was 18.4%. Within this category, the highest rates were observed for dryness in eyes (10.9%), eyes sensitive to light (5.9%), foreign body sensation (4.4%) and pain in eyes (4.1%).

PRK Study Data


Table 17: Cumulative Incidence of Non-Serious Protocol-Specified Adverse Events by Eye, (Intent-to-Treat)

(N=320) Adverse Event n (%) E Recurrent corneal erosion at 1 month or later 3 (0.9) 3 Any symptoms of dry eye that significantly affect comfort or activities of daily living at 6 months or later 64 (20.0) 64 Any symptoms of glare or haloes that significantly affect comfort or activities of daily living at 6 months or later 14 (4.4) 18 Clinical signs consistent with marked to severe dry eye at 6 months or later 1 (0.3) 1 Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later 59 (18.4) 128 1 - Pain in eyes 13 (4.1) 13 2 - Dryness in eyes 35 (10.9) 35 3 - Burning feeling in eyes 10 (3.1) 10 4 - Glare 2 (0.6) 2 5 - Eyes sensitive to light 19 (5.9) 19 6 - Halos (circle shapes around lights) 10 (3.1) 10 7 - Starbursts (star shapes around lights) 4 (1.3) 4 8 - Blurry vision 6 (1.9) 8 10 - Fluctuation (changes) in vision 6 (1.9) 6 11 - Difficulty focusing in dim or low light 2 (0.6) 2 12 - Watery Eyes / Tearing 5 (1.6) 5 13 - Foreign body sensation (feeling like something is in your eye) 14 (4.4) 14 Foreign body sensation at 1 month or later 23 (7.2) 29 Ghost/double images in the operative eye 30 (9.4) 31 Pain at 1 month or later 22 (6.9) 26 N = Number of eyes in ITT analysis set n = Number of eyes with events E = Number of events If an eye has multiple occurrences of an AE, the eye is presented only once in the respective count column (n) for the corresponding AE. Events are counted each time in the event (E) column. Denominators for percentages are the number of treated eyes

PRK Study Data


Table 18: Cumulative Incidence of Ocular Protocol Specified Adverse Event – Severity, (Intent-to-Treat)

Protocol Specified Mild Moderate Severe Adverse Event Category Adverse Event E n (%) n (%) n (%) Corneal edema between 1 week and 1 month after the procedure Corneal Oedema 1 1 (100.0) 0 ( - ) 0 ( - ) Corneal infiltrate or ulcer Corneal Infiltrates 2 2 (100.0) 0 ( - ) 0 ( - ) Recurrent corneal erosion at 1 month or later Corneal Erosion 3 2 (66.7) 1 (33.3) 0 ( - ) Any symptoms of dry eye that significantly affect comfort or activities of daily living at 6 months or later Dry Eye 64 37 (57.8) 23 (35.9) 4 (6.3) Any symptoms of glare or haloes that significantly affect comfort or activities of daily living at 6 months or later Glare 10 10 (100.0) 0 ( - ) 0 ( - ) Halo Vision 8 6 (75.0) 0 ( - ) 2 (25.0) Clinical signs consistent with marked to severe dry eye at 6 months or later Dry Eye 1 1 (100.0) 0 ( - ) 0 ( - ) Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later Dry Eye 35 12 (34.3) 19 (54.3) 4 (11.4) Eye Irritation 10 0 ( - ) 8 (80.0) 2 (20.0) Eye Pain 13 1 (7.7) 10 (76.9) 2 (15.4) Foreign Body Sensation

In Eyes 14 2 (14.3) 10 (71.4) 2 (14.3) Glarea 2 2 (100.0) 0 ( - ) 0 ( - ) Halo Visiona 10 2 (20.0) 6 (60.0) 2 (20.0) Lacrimation Increased 5 3 (60.0) 2 (40.0) 0 ( - ) Photophobia 19 2 (10.5) 15 (78.9) 2 (10.5) Photopsia 4 2 (50.0) 2 (50.0) 0 ( - ) Vision Blurreda 10 0 ( - ) 10 (100.0) 0 ( - ) Visual Impairment 6 2 (33.3) 4 (66.7) 0 ( - ) Foreign body sensation at 1 month or laterb Foreign Body Sensation

In Eyes 186 167 (89.8) 17 (9.1) 2 (1.1) Ghost/double images in the operative eyeb Diplopia 86 60 (69.8) 19 (22.1) 7 (8.1) Pain at 1 month or laterb Eye Pain 139 121 (87.1) 16 (11.5) 2 (1.4) E = Number of events n = Number of events in severity category Percentage is calculated as n/E. a The events glare (n=2, E=4), halos (n=2, E=6), and blurry vision (n=1, E=2) were reported by investigators as AEs based on VSARC responses. Although these events do not meet the protocol specified definition of “Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later”, Alcon considers that they are best accounted for in this table. b Events for these categories were identified through the VSARC questionnaire. Self-reported responses other than none were reported as adverse events.

PRK Study Data


Table 19: Cumulative Incidence of Ocular Protocol Specified Adverse Event – Resolution, (Intent-to-Treat)

Protocol Specified Resolved Not

Resolved Unknown Adverse Event Category Adverse Event E n (%) n (%) n (%) Corneal edema between 1 week and 1 month after the procedure Corneal Oedema 1 1 (100.0) 0 ( - ) 0 ( - ) Corneal infiltrate or ulcer Corneal Infiltrates 2 2 (100.0) 0 ( - ) 0 ( - ) Recurrent corneal erosion at 1 month or later Corneal Erosion 3 2 (66.7) 1 (33.3) 0 ( - ) Any symptoms of dry eye that significantly affect comfort or activities of daily living at 6 months or later Dry Eye 64 29 (45.3) 33 (51.6) 2 (3.1) Any symptoms of glare or haloes that significantly affect comfort or activities of daily living at 6 months or later Glare 10 6 (60.0) 4 (40.0) 0 ( - ) Halo Vision 8 4 (50.0) 4 (50.0) 0 ( - ) Clinical signs consistent with marked to severe dry eye at 6 months or later Dry Eye 1 1 (100.0) 0 ( - ) 0 ( - ) Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later Dry Eye 35 11 (31.4) 22 (62.9) 2 (5.7) Eye Irritation 10 4 (40.0) 4 (40.0) 2 (20.0) Eye Pain 13 4 (30.8) 7 (53.8) 2 (15.4) Foreign Body Sensation

In Eyes 14 6 (42.9) 8 (57.1) 0 ( - ) Glarea 2 2 (100.0) 0 ( - ) 0 ( - ) Halo Visiona 10 10 (100.0) 0 ( - ) 0 ( - ) Lacrimation Increased 5 0 ( - ) 3 (60.0) 2 (40.0) Photophobia 19 7 (36.8) 10 (52.6) 2 (10.5) Photopsia 4 4 (100.0) 0 ( - ) 0 ( - ) Vision Blurreda 10 4 (40.0) 6 (60.0) 0 ( - ) Visual Impairment 6 4 (66.7) 2 (33.3) 0 ( - ) Foreign body sensation at 1 month or laterb Foreign Body Sensation

In Eyes 186 156 (83.9) 28 (15.1) 2 (1.1) Ghost/double images in the operative eyeb Diplopia 86 84 (97.7) 0 ( - ) 2 (2.3) Pain at 1 month or laterb Eye Pain 139 94 (67.6) 40 (28.8) 5 (3.6) E = Number of events n = Number of events in resolution category Percentage is calculated as n/E. a The events glare (n=2, E=4), halos (n=2, E=6), and blurry vision (n=1, E=2) were reported by investigators as AEs based on VSARC responses. Although these events do not meet the protocol specified definition of “Any symptom marked moderate or severe on the VSARC questionnaire at month 6 or later”, Alcon considers that they are best accounted for in this table. b Events for these categories were identified through the VSARC questionnaire. Self-reported responses other than none were reported as adverse events.

PRK Study Data


The cumulative rates of non-protocol specified AEs are presented in Table 20. The most frequently reported event was corneal opacity, with a rate of 5.6%. All cases with the exception of 1 eye were reported as resolved. One incidence of corneal opacity/corneal haze at Month 6 was device related. The event was assessed as mild and resolved with treatment by Month 12.

Table 20: Cumulative Incidence of Ocular Non-Serious Adverse Events by Eye (Intent-to-Treat)

PRK Study Data


Table 21 presents the summary of corneal haze by severity throughout the study. The highest rate of grade 1 or greater corneal haze was at Month 1 (9.7%) and progressively decreased through Month 12 to 1.0%.

Table 21: Corneal Haze by Severity and Visit (Intent-to-Treat)

PRK Study Data


Contrast sensitivity (the ability to see objects that may not be outlined clearly or that do not stand out from their background) is usually tested under various lighting conditions. Below are the results of contrast sensitivity for subjects in the study:

• At 12 months after PRK:

o 88 out of 311 eyes had significantly better contrast sensitivity in dim light with a glare source

o 70 of 311 eyes had significantly better contrast sensitivity in dim light without a glare source

o 42 of 311 eyes had significantly better contrast sensitivity in bright light with a glare source

o 33 of 311 eyes had significantly better contrast sensitivity in bright light without a glare source

o 19 out of 311 eyes had significantly worse contrast sensitivity in dim light with a glare source

o 20 of 311 eyes had significantly worse contrast sensitivity in dim light without a glare source

o 21 of 311 eyes had significantly worse contrast sensitivity in bright light with a glare source

o 10 of 311 eyes had significantly worse contrast sensitivity in bright light without a glare source

o 204 out of 311 eyes had no significant change in contrast sensitivity in dim light with a glare source

o 221 of 311 eyes had no significant change in contrast sensitivity in dim light without a glare source

o 248 of 311 eyes had had no significant change in contrast sensitivity in bright light with a glare source

o 268 of 311 eyes had had no significant change in contrast sensitivity in bright light without a glare source

PRK Study Data


4.6. Patient Reported Outcomes Results for the Visual Symptoms Associated with Refractive Correction (VSARC) questionnaire are presented in Table 22. At all postoperative visits, most subjects rated their symptoms as none or mild. At Month 6, 4.4% or less of subjects reported moderate or severe symptoms. Table 22: Visual Symptoms Associated with Refractive Correction Questionnaire

by Subject (Intent-to-Treat)

PRK Study Data


PRK Study Data


Table 23 presents the outcomes of the Refractive Status and Vision Profile (RSVP) questionnaire.. At Month 6, the mean score shows that vision-related quality of life did not worsen following PRK.

Table 23: Descriptive Statistics for RSVP Subscales by Visit by Subject (Intent-to-Treat)

PRK Study Data


4.7. Overall Conclusion The primary effectiveness and safety objectives of the C-10-084 study were met. No unanticipated safety risks were revealed. The results of this study establish the effectiveness and safety of the ALLEGRETTO WAVE EYE-Q excimer laser system for the PRK treatment of myopia up to - 6.0 D sphere and MRSE with or without astigmatism up to - 3.0 D cylinder.

Preparation Of Devices, Instruments And Material


5. PREPARATION OF DEVICES, INSTRUMENTS AND MATERIAL Prepare all material, instruments and devices necessary for surgery. Arrange them conveniently for surgeon and his/her assistant(s) to provide a good workflow during surgery. Figure 5: Suggestion For OR Arrangement



WARNING

Please also refer to the Procedure Manual, the User Manual and to its addendums of the WaveLight® EX500 laser system.

6. TREATMENT PLANNING AND DATA ENTRY Observe all inclusion and exclusion criteria, adverse event, indication, contraindication, warning and precaution information given in this manual. The treatment plan and data entry is made and controlled remotely at the laser system. For details regarding data entry and treatment programming please also refer to the User Manual.

6.1. Treatment Plan And Data Entry If data transfer is not available, enter all mandatory entries in the “Refractive and Corneal Details” section or the rated area in “Diagnostic / Basic Diagnostics” and determine / check treatment parameter in Treatment Data section. Manual entry does not include the registration option or centration on corneal apex using ALLEGRO Topolyzer VARIO data. Transfer treatment relevant diagnostic data and entered patient and eye data from the WaveLight GmbH diagnostic device to the WaveLight® EX500 laser system and the planning station.

• Check the selected infrared image and the related centration data for repeatability in comparison to all other exams imported.

• Verify the transferred examination data and complete any additional entries. Double-check with the patient and assisting personnel to ensure that there are no possible restrictions for the treatment. It is the sole responsibility of the operating surgeon to ensure that all data is accurate and that the treatment can be safely carried out. Save treatment plan with all entries and for later use or retrieval.



6.2. Parameters Determining Ablation The treatment is determined automatically by parameters entered in section “Refractive and Corneal Details” and “Treatment Design”. Parameters determining treatment are “Clinical”, “Vertex Distance (VD)”, “K-Readings”, “Optical Zone” (OZ) and Refractive Aim (planned “Target” refraction). Refraction:

Enter refraction parameters according to patient’s manifest refraction or to your preferred refraction for treatment. Modify refraction according to your own nomogram, if available. Enter target refraction (aim), if not targeted for emmetropia. Correction treatment will be calculated as difference between entered refraction (in section “Diagnostic”) and target refraction (entered in section “Treatment Planning”).

NOTE

Refraction Entry And Vertex Distance

Input of refraction is possible in plus- or minus-cylinder notation. The software converts the entries automatically into a treatment program that will have the least amount of central ablation depth for the intended correction. Enter the Vertex Distance measured during refraction examination. This value will influence treatment, as the correction will be applied on the corneal plane instead of the spectacle plane. It is recommended to measure the vertex distance exactly in patients with deep seated eyes.



CAUTION

Proven Parameter Range

Safety and effectiveness of treatments have not been proven for all available optical zones evaluated during the clinical trials that led to the approval of the WaveLight® EX500 laser system. Safety and effectiveness have not been proven below and above 6.5 mm optical zones.

CAUTION

Nomogram Use

If a nomogram shall be applied, changes according to the nomogram must be made in Refraction entries. Notes about the change according to nomogram should be made in the patient’s files. Depth of ablation and residual stroma thickness must be calculated and noted before application of any nomogram.

Optical Zone:

The optical zone is displayed and entered in millimeters. Default optical zone is always 6.5 mm. Check the optical zone size with the largest physiologic pupil size measured under mesopic conditions and resulting ablation depth (see Procedure Manual, chapter “Ablation Depth And Remaining Stromal Thickness”).



CAUTION

Remaining Thickness

Exceeding the minimum thickness of 250 microns increases the risk for corneal ectasia following treatment.

6.3. Feasibility Checks Check if all mandatory entries with patient’s data, examination and treatment data are filled correctly. Check resulting correction and ablation depth and match them again with patient’s eye and treatment plan data of the patient’s file. Optical zone and / or refractive parameters may have to be changed, if conflicts are determined in the feasibility checks.

6.3.1. Ablation Depth And Remaining Stromal Thickness Check resulting remaining stromal thickness indicated as “Residual Stroma” or “Res. Stroma”. A warning will be displayed as soon as the set minimum value is be violated by actual treatment parameter. The manufacturer’s setting for the alert level is 250 µm.



6.4. Confirm And Save Data The “Database Portal Software” of the laser system provides an “Overview”. This window will display the planed treatments and the related summary of the important treatment plan information, possible warnings and messages for final check and confirmation. Double-check all data, messages and warnings before confirming treatment plan to accept data and possible warnings or consider a different plan for the patient. Make sure a valid WaveCard™ is inserted. Press on start to initiate a treatment sequence. The “Database Portal Software” will change to treatment screen and show treatment data, the live images of the eye and eyetracker, the pachymetry and the laser status. The refraction data (correction) and the chosen optical zone will be displayed on the monitor screen. All refraction values are at spectacle plane. The vertex distance will be the one entered with the patient’s refraction. Additional info and warnings will be displayed on the monitor screen only throughout the treatment.

Index


7. INDEX Page Page Ablation Depth .................................... 52 Ablation Details .................................. 18 Aborted Treatment .............................. 17 Confirm Data ...................................... 53 Contraindications ................................ 11 Copyright .............................................. 6 Data Analysis ..................................... 22 Data Entry .......................................... 49 Database Portal Software Version ........ 2 Decreased Vision In One Eye ............. 13 Demographics Parameters ................. 23 Effectiveness Results ......................... 27 Feasibility Checks ............................... 52 Indications For Use ......................... 9, 11 Intended Use ........................................ 9 Nomogram Use .................................. 51 Optical Zone ....................................... 19 Optical Zone Parameters .................... 51 Overall Conclusion ............................. 47 Parameters Determining ..................... 50

Patient Reported Outcomes................ 44 Patient Selection ................................. 14 Post Procedure ................................... 20 Precautions ........................................ 12 Preparation ......................................... 48 Procedure Steps ................................. 15 Refraction Entry .................................. 50 Refraction Parameters ........................ 50 Remaining Stroma .............................. 52 Residual Stroma ................................. 52 Safety Results .................................... 34 Save Data ........................................... 53 Study Design ...................................... 21 Study Objective .................................. 21 Treatment Interruption ........................ 17 Treatment Planning ............................ 49 Treatment Profiles .............................. 19 Using The Procedure Manual ............... 3 Vertex Distance .................................. 50 Warnings ............................................ 13


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