Hyperopia Correction Using the NTK Optimal Keratoplasty (Opti-K) System
Phase: NA
Conditions: Hyperopia
Sponsor: NTK Enterprises, Inc.

CONFIDENTIAL 
Hyperopia Correction using the  
NTK Optimal Keratoplasty (Opti-K™) System 
 
 
 
PROTOCOL NUMBER:  
OK-001 
 
DATE: 
 
 
 
September 2, 2010 
 
Amended:  
 
 
January 6, 2016 
 
VERSION:  
 
 
1.4 
 
SPONSOR:  
 
 
NTK Enterprises, Inc. 
2800 N. Dallas Parkway, Suite 100 
Plano, TX  75093 
Telephone: (831) 869-1384 
FAX:  
(512) 992-1060 
 
 
MEDICAL MONITOR:  
Harry G. Glen, MD 
 
 
 
 
 
Telephone: (561) 252-0946 
                                                   Email: oceans11@bellsouth.net 
 
 
 
CLINICAL MONITOR:  
NTK or NTK representative 
 

CONFIDENTIAL 
Investigator Signature Page 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
My signature below certifies that I have read this protocol and agree to conduct the study 
in accordance with the specified procedures. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR NAME (Printed):  
 
 
 
Date:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR SIGNATURE: 
 
 
 
 
Date: 

CONFIDENTIAL 
TABLE OF CONTENTS 
 
1.0 Background ............................................................................................................... 4 
3.0 Objectives ................................................................................................................... 5 
4.0 Safety and Efficacy Endpoints ................................................................................. 5 
5.0 Study Design .............................................................................................................. 6 
6.0 Subject Population .................................................................................................... 7 
6.1 Inclusion Criteria ................................................................................................. 7 
6.2 Exclusion Criteria ................................................................................................ 8 
7.0 Study Duration and Examination Schedule ............................................................ 9 
7.1 Study Duration ..................................................................................................... 9 
7.2 Examination Schedule ....................................................................................... 10 
7.2.1 Primary Treatment ........................................................................................ 10 
8.0 Study Procedures..................................................................................................... 10 
8.1 Bilateral and Fellow Eye Treatment ................................................................ 10 
8.2 Preoperative Evaluation (Day -30 to Day 0) .................................................... 10 
8.2.1 Screening Eye Examination .......................................................................... 11 
8.2.2 Contact Lens Discontinuation and Stability Check ...................................... 12 
8.2.3 Concomitant Medication ............................................................................... 12 
8.3 Opti-K™  Treatment Nomogram ..................................................................... 12 
8.3.1 Primary Treatment (Treatment #1) ............................................................... 12 
8.4 Outpatient Opti-K™  Surgical Procedure (Day 0) ......................................... 14 
8.4.1 Treatment Procedure – Device and Materials Preparation ........................... 14 
8.4.2 Treatment Procedure – Patient Preparation .................................................. 14 
8.4.3 Treatment Procedure - Pre-Treatment Centration ......................................... 15 
8.4.4 Primary Treatment Procedure ....................................................................... 17 
8.4.5 Treatment Procedure - Post-Treatment Centration Measurement ................ 17 
8.4.7 Operative Report ........................................................................................... 18 
8.4.8 Postoperative Care ........................................................................................ 18 
8.5 Follow-Up Visits (1 Day, 1 Week, 1, 3, 6, 9, 12 and 24 months) .................... 18 
8.6 Retreatment ........................................................................................................ 20 
8.7 Safety Monitoring .............................................................................................. 20 
8.8 Post-Study Procedures ....................................................................................... 20 
8.9 Device  Accountability ....................................................................................... 20 
8.10 Early Withdrawal from Study ........................................................................ 20 
9.0 Data Analysis and Statistical Considerations ........................................................ 20 

CONFIDENTIAL 
9.1 Sample Size ......................................................................................................... 21 
9.2 Analysis by Indication ....................................................................................... 22 
9.3 Accountability .................................................................................................... 22 
9.4 Screening ............................................................................................................. 23 
9.5 Subject Characteristics ...................................................................................... 23 
9.6 Primary Efficacy Criteria ................................................................................. 23 
9.8 Clinical Safety Endpoint Criteria ..................................................................... 25 
9.8.1 Adverse Events and Complications .............................................................. 25 
9.8.2  Key Safety Parameters ................................................................................. 26 
9.9 Other Outcome Measures ................................................................................. 26 
9.10 NEI-RQL-42 ..................................................................................................... 26 
9.11 Subjective Symptom Questionnaire ............................................................... 28 
9.12 Retreatments .................................................................................................... 28 
9.13 Dropouts/Lost-to-Follow-up ........................................................................... 28 
9.14 Poolability ......................................................................................................... 28 
9.15 Missing data ...................................................................................................... 28 
10.0 Ethical and Regulatory Considerations ................................................................. 29 
10.1 Informed Consent ............................................................................................ 29 
10.2 Institutional Review Board ............................................................................. 29 
10.3 Complications and Adverse Events ................................................................ 29 
10.3.1 Serious and Unanticipated Adverse Device Effects ................................... 30 
10.4 Monitoring ........................................................................................................ 31 
10.5 Source Documents / Case Report Forms ....................................................... 31 
10.6 Deviation from the Protocol ............................................................................ 31 
APPENDIX A:  STUDY FLOW CHART AND EXAMINATION SCHEDULE .......... 33 
APPENDIX B:  CFR 50.25 - ELEMENTS OF INFORMED CONSENT ................... 35 
APPENDIX C: TEST METHODS .................................................................................. 36 
 
 
1.0 
BACKGROUND 
This study is being conducted to evaluate the safety and effectiveness of an optimal 
keratoplasty treatment using the NTK Optimal Keratoplasty (Opti-K™)  system for 
treating hyperopic manifest refractive errors. 
 
 
 

CONFIDENTIAL 
2.0 
DEVICE  DESCRIPTION 
  
The device used in this study is the NTK Optimal Keratoplasty (Opti-K™) System. The 
Opti-K™ System is a continuous wave (cw) thulium fiber laser (TFL) device for 
irradiation of corneas that are in contact with a sapphire applanation window/suction ring 
(SAWSR) for protection of the cornea epithelium from thermal damage. 
 
The device includes a continuous wave (cw) thulium fiber laser (TFL) whose output 
beam is divided by beamsplitters into 4 “beamlets” that are transmitted through optical 
fibers and directed onto the cornea in a symmetrical square ring pattern (See Section 8.3). 
The laser output is at 1.93 µm wavelength.  The laser is typically operated with a total 
delivered power (from the optical fibers) between 0.9 to 1.8 W for a period of 150 ms. 
The delivered energy (from the optical fibers) is in the range of 30 to 60 mJ/spot.  (When 
uncoated sapphire windows are used in a sapphire applanation window/suction ring, the 
actual delivered energy to the cornea is reduced by Fresnel reflection losses – ca. 9% 
total - at the air/sapphire and sapphire/cornea interfaces.) 16 spots are delivered in 
symmetrical arrays (See Section 8.3).  
 
 
3.0 
OBJECTIVES 
The primary objective of this study is to investigate the safety and effectiveness of the 
NTK Enterprises Optimal Keratoplasty (Opti-K™) System for performing optimal 
keratoplasty for the treatment of hyperopic manifest-based refractive errors to achieve 
temporary improvement in distance uncorrected visual acuity. 
 
Data from this study will be used to support a marketing application to obtain FDA 
approval for use of the Opti-K™ System for performing optimal keratoplasty treatments 
for hyperopia correction. 
 
4.0 
SAFETY AND EFFICACY ENDPOINTS 
The primary efficacy parameters will be refractive predictability, refractive stability, and 
uncorrected distance visual acuity.  
 
Safety assessments will include a tabulation of complications and adverse events, patient 
symptoms, loss of best spectacle-corrected visual acuity, changes in contrast sensitivity, 
and induced astigmatism. Quality of vision will be assessed using the National Eye 
Institute Refractive Error Quality of Life Instrument (NEI-RQL-42).1   
 
Specific methods of analysis are provided in Section 9.0, Data Analysis.  
 
 
                                               
1 National Eye Institute Refractive Error Quality of Life Instrument (NEI-RQL-42™), Version 1.0; Rand Institute, 
2001.  

CONFIDENTIAL 
5.0 
STUDY DESIGN 
This safety and effectiveness study is a prospective, single arm, non-randomized, 
unmasked multicenter clinical study in which the primary control is the preoperative 
status of the treated eye. 
 
The initial (feasibility) clinical study will be limited to three clinical sites with a total 
enrollment of 40 patients. One objective of the initial clinical study will be to refine the 
treatment nomogram in preparation for an expanded clinical study. Information from both 
the International Clinical Study and the initial U. S. Clinical Study will be used to 
determine the final treatment nomogram which will be then be used for the expanded  
U.S. Clinical Study. The final treatment nomogram will not be modified after the 
expanded U. S. Clinical Study begins. The expanded study will include additional clinical 
sites and will bring the total enrollment to a sufficient number of patients to have 350 
treated eyes (of which at least 300 eyes will be in the completed cases cohort).  All 
treated eyes (bilateral Treatments plus unilateral Treatments, if any) will be included in 
the study; safety and effectiveness analyses will be completed using all treated eyes. 
Initial patient enrollment is estimated to be 3 to 6 months following study initiation. Each 
patient will be followed for 24 months following treatment. The total duration of this 
study is estimated to be 36 months. 
 
All study eyes will be evaluated at the screening/baseline examination, Day 0 (Opti-K™  
treatment day), and 1 day, 1 week, and 1, 3, 6, 9, 12, 18, and 24 months after the Opti-
K™  treatment.  Corneal topography, manifest refraction, and measurements of 
uncorrected and best spectacle-corrected visual acuity will be obtained at baseline and at 
appropriate times after the Opti-K™  treatment to evaluate the effectiveness of the 
treatment.  Safety monitoring throughout the study will include observations at 
appropriate times for subjective complaints, complications, and adverse events, as well as 
clinically significant findings on ophthalmic examination, dilated fundus examination, 
slit lamp examination, specular microscopy, and contrast sensitivity testing.  Patient 
questionnaires will be used to evaluate subjective visual complaints, quality of vision, 
and quality of life preoperatively and postoperatively. 
 

CONFIDENTIAL 
6.0 
SUBJECT POPULATION 
This study is a multicenter study that will be conducted initially at three (3) 
investigational sites located in the U.S. with forty (40) patients enrolled in the initial pilot 
study phase. Each investigator is expected to contribute approximately 50% of the study 
population in the pilot study. Upon receipt of FDA approval, the study will be expanded 
to up to 10 investigational sites with up to 350 eyes treated to provide 300 evaluable eyes.  
In the expanded study, each investigator is expected to contribute at least 20 eyes to the 
study and no investigator should enroll more than 25% of the study population (88 eyes 
total). Permission from the sponsor is required to exceed enrollment of 88 eyes at any 
single site. 
 
6.1 
Inclusion Criteria 
Subjects in whom the study eye meets all of the following criteria are candidates for this 
study: 
1. Male or Female 
2. Any race 
3. Patient is at least 40 years old. 
4. Patient has bilateral sight with at least one eye with low hyperopia within the 
specified manifest refraction range as follows:  
a. Sphere between +1.0 to +2.5 D; 
b. Absolute Cylinder ≤ 0.75 D; and, 
c. MRSE between +0.63 to +2.5 D. 
5. Documented stable refraction defined as 0.5 D or less change in MRSE per year 
for 12 months or longer prior to primary Opti-K™  treatment, based on 
refractions, medical records or prescription history. 
6. Able to tolerate full cycloplegic refraction while not under cycloplegia. 
7. Distance uncorrected visual acuity (D-UCVA) between 20/63-2 and 20/32+2  
(i.e., from 58 to 77 letters on an ETDRS chart)  
8. Distance best spectacle corrected visual acuity (D-BSCVA) of 20/40 or better 
(i.e., 70 letters or better on an ETDRS chart in both eyes. 
9. Patient has normal videokeratography (i.e., without distorted or unclear corneal 
mires). 
10. Is not a contact lens wearer or, if wearing contact lenses, has discontinued 
wearing contact lenses for the required period of time and completed the contact 
lens stability check as described below. 
a.  Contact Lens Wearers Only:  Demonstration of a stable refraction, 
defined as two manifest refractions that are within ± 0.5 D MRSE of each 
other as determined under the following conditions: 
i. The two refractions are performed at least 7 days apart; and, 
ii. Contact lenses are not worn for at least the specified period of time 
prior to the first refraction used to establish stability and through 
the day of surgery: 
 
 

CONFIDENTIAL 
Contact Lens Type 
Minimum Discontinuation Time 
Soft 
3 Days 
Soft Extended Wear 
1 Week 
Soft Toric 
2 Weeks 
Rigid gas permeable 
2 Weeks 
 
11. Patient is willing and able to comply with all pre-treatment and follow-up 
requirements, including the ability to read English to complete the NEI-RQL 
questionnaire  
12. Patient understands the nature of the procedure, as well as potential risks or 
limitations of the treatment, and provides informed consent.  
6.2 
Exclusion Criteria 
Subjects in whom the study eye meets any of the following criteria are will be excluded 
from this study: 
1. Latent hyperopia > 1.0 D (i.e., baseline MRSE and CRSE should not differ by 
more than 1.0 D) 
2. Nystagmus 
3. Previous intraocular or corneal surgery (except strabismus surgery is 
permitted) 
4. Significant conjunctivochalasis 
5. Residual, recurrent or active ocular disease or corneal abnormality, including 
any of the following: 
a. corneal diameter < 9 mm 
b. central corneal thickness < 500 µm 
c. moderate to severe dry eye disease 
d. uncontrolled uveitis;  
e. severe blepharitis;  
f. lagophthalmos;  
g. glaucoma; 
h. intraocular pressure > 21 mm Hg;  
i. cataract;  
j. history of uveitis;  
k. corneal shape disorders (keratoconus, keratoglobus, pellucid marginal 
degeneration, significant irregular corneal astigmatism, topography 
with irregular mires, etc.); 
l. history of herpes zoster/simplex keratitis                       
6. Cloudy cornea or cloudy anterior chamber 
7. Allergy to anesthetics or postoperative medications 
8. History or current evidence of chronic allergic reactions, tearing and/or ocular 
irritation that might confound the outcome or increase the risk of the study. 
9. The use of systemic medications that may confound the outcome or increase 
the risk of the study, including, but not limited to: corticosteroids, 

CONFIDENTIAL 
antimetabolites, amiodarone, isotretinoin, sumatriptan, or other medications 
that may affect wound healing. 
10. Patients with a recent history (within one week prior to treatment) of using 
ophthalmic medications containing preservatives (benzalkonium chloride, 
etc.) and/or other ocular drugs that are cytotoxic. 
11. Acute or chronic illness that might increase the risk or confound the outcome 
of the study (e.g., diagnosed autoimmune disease, systemic connective tissue 
disease, clinically significant atopic disease, diabetes mellitus with ocular 
involvement, etc.) 
12. Pregnant, planning to be pregnant or lactating women 
13. Patients participating in other ophthalmic clinical trials during this clinical 
investigation 
14. Persons who, in the determination of the investigator, are not competent to 
understand the procedure or the actions asked of them as research subjects or 
have unrealistic expectations. 
15. Persons who may not be able to complete the requirements of returning to the 
investigator’s clinic over the period of the study, or who may be difficult to 
locate or contact on short notice. This does not preclude vacations or travel. 
16. Persons who cannot achieve corneal applanation using the SAWSR device or 
cannot tolerate application of the SAWSR device or who cannot remain 
motionless for at least 5 seconds after verifying proper SAWSR mounting. 
17. Patients who are likely to be exposed to high levels of ultraviolet radiation 
(from sunlight, tanning lights, etc.) without protective eyewear during the one 
year period following Opti-K™  treatment. 
18. Presence or history of any other condition or finding that, in the opinion of the 
investigator, makes the patient unsuitable as a candidate for Opti-K™  
treatment or study participation or may confound the outcome of the study 
19. Mesopic pupil diameter >5.6 mm 
20. Presence of a pupil irregularity (e.g., decentered pupil or irregular shape) in 
the eye to be treated that could predispose the eye to a centration error during 
the treatment. 
 
7.0 
STUDY DURATION AND EXAMINATION SCHEDULE 
7.1 
Study Duration 
The study duration is scheduled for a total of 24 months for all study subjects.  
 
The sponsor may file a Pre-Market Approval (PMA) application when refractive stability 
for the cohort has been determined and 80% of the eyes in the cohort have completed the 
confirmatory examination that is the next scheduled visit after refractive stability for the 
cohort is achieved.  
If the PMA is filed before study conclusion, subjects enrolled in the study will continue 
through the Month 24 visit unless permission to conclude the study early is requested and 
received from FDA. 
 

CONFIDENTIAL 
7.2 
Examination Schedule 
7.2.1 Primary Treatment 
All patients are expected to return for follow-up examinations at 1 day, 1 week, and 1, 3, 
6, 9, 12, 18 and 24 months post-primary treatment. Recommended visit windows for the 
primary treatment are: 
§ Screening: 
-30 to -1 days 
§ Primary Treatment: 
Day 0 
§ 1 Day (1D): 
 
1 to 3 days 
§ 1 Week (1W):  
5 to 9 days 
§ 1 Month (1M:  
3 to 5 weeks 
§ 3 Months (3M): 
10 to 14 weeks 
§ 6 Months (6M): 
21 to 26 weeks 
§ 9 Months (9M): 
35 to 43 weeks 
§ 12 Months (12M): 
11 to 14 months 
§ 18 Months (18M): 
17 to 20 months 
§ 24 Months (24M): 
23 to 27 months 
 
All final exam procedures will be completed at the Month 24 visit. If a subject drops out 
or is withdrawn from the study before completing the Month 24 examination, a Final 
Exam should be completed whenever possible, following the Month 24 Final Exam 
procedures. If a final examination cannot be performed, the last scheduled examination 
completed by the subject will be considered the final examination.  
 
 
8.0 
STUDY PROCEDURES 
Subjects who elect to participate in this study will complete the study as outlined below. 
All tests and measurements will be obtained in accordance with the procedures specified 
in this protocol. General instructions for use of Opti-K™  System are provided in the 
Instructions for Use for the device. If there are differences between the Instructions for 
Use and this protocol, the instructions provided in this protocol should be followed. 
 
8.1 
Bilateral and Fellow Eye Treatment 
Patients in the initial clinical study will be treated unilaterally in their dominant eyes.  
Fellow eyes cannot be treated in this study. Fellow eyes requiring refractive treatment 
may be treated with any other approved technology. Data will be captured on the non-
study fellow eye and may be presented as a control. 
 
8.2 
Preoperative Evaluation (Day -30 to Day 0) 
All screening examination procedures will be performed by the investigator or trained 
personnel working under the investigator’s supervision. Study candidates who are 
evaluated preoperatively by referring doctors will sign a consent form and have the 
screening procedures repeated preoperatively by study personnel.  Screening data from 
referring doctors will not be used as the screening data for the study, except to document 

CONFIDENTIAL 
preoperative refractive changes. Procedures or evaluations that were performed by study 
personnel during routine non-study visits may be used for the screening examination if 
the testing was completed: (1) within the 30 day screening window; (2) in accordance 
with the protocol requirements; and, (3) as part of the investigator’s usual and customary 
examination procedures.  Subjects will sign a consent form before any procedures or tests 
specific to the study protocol are performed. 
 
8.2.1 Screening Eye Examination  
Potential Opti-K™  candidates will undergo a complete screening eye examination to 
determine their eligibility for study participation.  Demographics and a complete ocular 
history, medical history and medication history will be obtained.  The complete eye 
examination and ocular history will include: 
§ UCVA distance (ETDRS chart) 
§ UCVA near 
§ BSCVA distance (ETDRS chart) 
§ BSCVA near 
§ Binocular UCVA distance 
§ Binocular UCVA near 
§ Manifest refraction 
§ Cycloplegic refraction 
§ Topography/Keratometry  
§ Pachymetry 
§ Aberrometry (report as 6 mm, 8th order) with pupil dilated to at least 6.5 mm 
• Intraocular pressure  
• Slit lamp examination of the cornea, anterior chamber and lens 
• Mesopic pupil diameter 
• Dilated fundus examination 
• Contrast sensitivity [substudy at AEC clinical site only] 
• Specular microscopy [substudy at AEC clinical site only] 
• NEI-RQL-42 questionnaire 
• Subjective complaint questionnaire 
Topography, manifest refraction, and visual acuities should be done before dilation and 
before the completion of the cycloplegic refraction and any other potential tear 
disruptions tests (e.g., IOP measurement) so that the tear film is not altered. Aberrometry 
should be performed after dilation and before applanation tonometry. 
 
Other optional diagnostic tests may be performed at the investigator’s discretion (e.g., 
corneal hysteresis, OCT, topography and wavefront measurements with other devices 
such as the Oculyzer and iTrace) to further evaluate the subject for refractive surgery. 
Optional diagnostic tests should be performed after the examination requirements of the 
study have been completed. 
 
Manifest refractions may be recorded on the source documents in the investigator’s usual 
notation (plus or minus cylinder format) and will be recorded onto the case report forms 
using the standard notation (plus cylinder) designated by the sponsor.  

CONFIDENTIAL 
 
8.2.2 Contact Lens Discontinuation and Stability Check 
Contact lens wearers should discontinue contact lens wear for at least the following 
period of time before the screening examination and continue to abstain from contact lens 
wear through the day of surgery for the primary treatment: 
• At least 3 days for spherical soft lenses, 
• At least 1 week for soft extended-wear lenses, 
• At least 2 weeks for soft toric 
• At least 2 weeks for rigid gas-permeable lenses 
Contact lens wearers will complete an additional examination that is at least 7 days after 
the screening examination to confirm refractive stability after contact lens 
discontinuation. A manifest refraction will be performed at this visit. Contact lens 
wearers should exhibit a stable refraction, defined as two manifest refractions performed 
at least 7 days apart that are within ± 0.5 D MRSE of each other. If a difference greater 
than ± 0.5 D MRSE is observed, the subject should either: (1) be declared a screening 
failure; or, (2) be examined at additional visits until stability (<0.50 D MRSE difference 
between consecutive examinations at least 7 days apart) is attained. 
 
Contact lens wear in the Opti-K™ treated eye may not be resumed after the treatment 
during the study period. 
 
8.2.3 Concomitant Medication 
Subjects are permitted to take prescribed or non-prescription medications and 
supplements before and after the Opti-K™  procedure at the discretion of the 
investigator. 
 
 
8.3 
Opti-K™  Treatment Nomogram 
Optimal keratoplasty (Opti-K™ ) treatment outcomes are a function of laser irradiation 
conditions, as well as patient factors such as age and wound healing response.  Initially, 
the treatment nomogram will be based on visual acuity improvements observed in an 
international clinical study on in vivo human eyes.  However, this initial treatment 
nomogram is based on a small number of patient eyes with a relatively short follow-up 
time (3 to 9 months), so the nomogram will be improved as more eyes are treated and 
examined at longer follow-up times.  
 
8.3.1 Primary Treatment (Treatment #1) 
For intended primary effective refractive change (ΔMRSE), 16 spots of laser energy are 
delivered to the cornea in two concentric 8-spot rings of 6.0 mm and 7.2 mm centerline 

CONFIDENTIAL 
diameters, with spots on radials, as shown in Figure 8.3.1-1 below.  Laser energy is 
delivered in sets of 4 spots per irradiation as follows: 
1) 4 spots (at 0°, 90°, 180° and 270°) on the inner ring (6.0 mm diameter), 
2) 4 spots (at 45°, 135°, 215° and 305°) on the inner ring (6.0 mm diameter), 
3) 4 spots (at 0°, 90°, 180° and 270°) on the outer ring (7.2 mm diameter), and 
4) 4 spots (at 45°, 135°, 215° and 305°) on the outer ring (7.2 mm diameter).  
 
0
45
90
135
180
225
270
315
 
Figure 8.3.1-1:  16-Spot Opti-K™  primary treatment pattern.  Concentric rings are at 1 
mm diameter intervals and are centered with respect to the pupillary center; treatment 
spots are located symmetrically and radially on rings at 6.0 and 7.2 mm centerline 
diameters.  
All primary Treatments for patient eyes with hyperopia with MRSE in the range of 
+1.0 to +2.5 D should be completed at a primary Treatment energy density F of 
between 40 and 48 mJ/spot as noted below.   

CONFIDENTIAL 
 
Pre-Tx MRSE (D)   
F’ (mJ/spot) 
+1.00 
40 
+1.13 
44 
+1.25 
48 
+1.38 
48 
+1.50 to +2.50 
48 
 
Table 8.3.2-1:  Primary treatment nomogram for Treatment pattern #1 (6.0/7.2 mm 
diameter rings) for eyes with hyperopia with pretreatment MRSE in the range of +1.0 to 
+2.5 D 
 
8.4 
Outpatient Opti-K™  Surgical Procedure (Day 0) 
8.4.1 Treatment Procedure – Device and Materials Preparation 
Prior to the procedure, the NTK Opti-K™  System should be in proper working order.  
This is confirmed by turning on the NTK Opti-K™  System, allowing it to initialize and 
then performing laser energy calibrations.  All calibrations are to be performed by a 
Sponsor representative.  The system is described in Section 2.0. 
 
Recommended supplies for use during the surgical procedure include: 
• Topical anesthetic  - preservative-free 0.5% proparacaine HCl – freshly obtained 
and stored in a refrigerator until use 
• Irrigating solution –  solute-free water 
• Anti-inflammatory medication – Prolensa (bromfenac ophthalmic solution 0.07%, 
Ista Pharmaceuticals, Irvine, CA) 
• Artificial tears – PF Blink Tears (Abbott Medical Optics, Santa Ana, CA) 
Equipment [sapphire applanation window assembly, etc.] that will touch ocular surfaces 
should be cleaned and disinfected using alcohol (ethanol) prior to use. The cleaned 
surfaces should be dried thoroughly using compressed air immediately following 
disinfection. 
8.4.2 Treatment Procedure – Patient Preparation 
Prior to patient preparation, the physician should instruct the patient regarding the 
treatment and what to expect, including a rehearsal of fixation and SAWSR placement. 
The patient shall lie down in a reclining position with eyes looking upward at the flashing 
fixation light.  The fellow eye should be covered with an occlusive patch. Preoperative 
sedation or anti-anxiety medication may be given at the investigator’s discretion or if 
requested by the patient. One drop of a topical anesthetic (preservative free 0.5% 

CONFIDENTIAL 
proparacaine HCl – freshly obtained and stored in a refrigerator until use) shall be 
instilled into the eye to be treated approximately two minutes pre-treatment.  The patient 
should close his or her eyelids for ca. 1 minute to obtain an anesthetic effect. Then, the 
lids should be opened.  
8.4.3 Treatment Procedure - Pre-Treatment Centration 
Fixation Light and Guide Circle Reticle 
A very functional fixation light has been developed using a miniature battery-powered 
light emitting diode (LED) mounted on the center of the iPad3 telescope objective lens.  
The mini LED (Part # APG1608CGKC/T; Kingbright Corporation, City of Industry, CA) 
emits light at 525 nm wavelength (green) and is battery operated. This provides a target 
on which patients can fixate their gaze.  A circular gunsight reticule was added to the 
sapphire application window as seen in Figure 8.4.3-1 to provide better visual cues for 
accurate centration.  To help minimize parallax, guide circles were added to the iPad3 
monitor. They are perfectly centered on the monitor itself and nearly the same diameters 
as the inner sapphire applanation window/suction (SAWSR) ring(small guide circle) and 
the inner illumination accessory ring (large guide circle), as shown in Figure 8.4.3-2.  
 
 
 
 
 
 
 
 
 
 
 
 
Figure 8.4.3-1. View from the iPad of the reticle aligned over a subject's 
cornea.  

CONFIDENTIAL 
 
 
Figure 8.4.3-2.  SAWSR assembly mounted on left eye (OS).  Two black guide circles (on 
the monitor) are nearly the same diameters, and are nearly concentric with, the inner 
SAWSR ring (small guide circle) and the inner illumination accessory ring (large guide 
circle).  A retroreflection of the fixation light from the sapphire window is visible as a 
green spot partly overlapping the pupil. 
 
By overlapping the rings formed by the SAWSR assembly with those of the monitor, the 
SAWSR assembly can be properly mounted on the eye without significant tilt or 
displacement. Mounting can be further facilitated if the iPad3 monitor is at the 
physician’s eye level. 
The fixation light is very visible to the patient as a small bright green spot until the 
cornea is applanated, at which time it appears larger and looks like a speckle pattern.  
There should be no problem in having the patient watch the fixation source through 
applanation and SAWSR assembly mounting. After mounting, the retroreflection of the 
fixation light shows that the sapphire window is normal (i.e., perpendicular) to the 
direction of propagation of the LED beam and hence to the optical axis of the telescope. 
A small angular misorientation (ca. 10° counterclockwise) is evident in Figure 8.4.3-2.  
The physician can watch for this and correct the angular orientation. 
 
 
 
 
 
 
 
 
 
 
 

CONFIDENTIAL 
 
8.4.4 Primary Treatment Procedure 
The physician should view the patient’s eye to be treated on the iPad monitor under good 
background illumination by turning on the light emitting diodes (LEDs) mounted on the 
sapphire applanation window/suction ring  assembly (SAWSR - see Section 2.0).  One 
drop of solute-free water should be placed on the cornea to prevent drying of the cornea 
and to aid hydration and lubrication. The patient should keep both eyes open and should 
look vertically upward at the fixation light.  If the patient has excessive eye motion (i.e., 
presents a moving target), the physician should postpone the treatment.  Physician 
counseling of the patient about the procedure should obviate nervousness that can cause 
excessive eye motion. 
The sapphire window with suction ring (SAWSR) should then be centered on the pupil 
using the round reticles in the window and  monitor screen.  Once in position, the 
window of the SAWSR should be applanated onto the cornea such that the tear film 
visibly spreads across it. At this point (when centration and applanation are achieved), an 
assistant holding a hand held vacuum pump squeezes the handle until the gauge measures 
20-30 cm/hg of  external pressure on the suction ring (at no time should the pump exceed 
a level that causes the central retinal artery to be occluded).. 
 
The evacuation port on the SAWSR should be projecting temporally when the SAWSR is 
mounted. The SAWSR is also equipped with four groups of three magnets per group. The 
center magnet of each group is used to engage the magnets on the fiber delivery holder 
(FDH) for primary treatment (Treatment). The physician should then position the fiber 
delivery holder (FDH) on the SAWSR so that its magnets (mounted on a collar on the 
FDH shaft) attach to the correct magnets (center of each set of 3 magnets for primary 
Treatment) on the SAWSR. The patient should be treated as soon as possible after 
mounting of the SAWSR and positioning of the FDH.  
 
The patient should be instructed not to move during the treatment (and preferably to hold 
his/her breath during the treatment), which takes ca. 2.5 seconds. The patient should not 
feel any pain during the treatment. It is important that the patient’s eye (and the patient) 
remain motionless during treatment.   
The physician should verify that the FDH is correctly mounted and then deliver laser 
light through the FDH by pushing the footswitch that starts an automated sequence of 
shutter opening/closing and fiber translation steps.  After the treatment is completed, 
vacuum pressure should be released and the FDH and SAWSR removed from the eye.  
One drop of Prolensa (bromfenac ophthalmic solution 0.07%, Ista Pharmaceuticals, 
Irvine, CA) should be instilled into the eye immediately post-Treatment.  Immediate post-
Treatment exams should then be completed. 
 
8.4.5 Treatment Procedure - Post-Treatment Centration Measurement 
As a post-treatment check on technique, decentration measurements are made after 
delivering treatments, using slit-lamp biomicroscope images obtained with a digital 

CONFIDENTIAL 
camera.  Images are printed out on 8½" X  11" paper, resulting in ca. 25X magnification.  
Treatment centers (TCs) and pupil centers (PCs) are located on these printouts; TCs are 
located by intersection of straight line connectors drawn between pairs of Treatment spots 
oriented 180° apart around Treatment rings and PCs are located by intersection of straight 
line connectors between pairs of pupil edges oriented 180° apart.  Distances between TCs 
and PCs are measured and converted to absolute distances using inner ring spot 
separations as a scale. Using a ruler with mm resolution and images with 25X 
magnification, a typical TC-PC distance can be located to ca. 0.04 mm absolute distance 
accuracy. 
 
8.4.7 Operative Report 
An immediate post-treatment report should be completed for all treated patients, and for 
those patients for whom a treatment was attempted but not completed.  The immediate 
post-treatment report should include information on intended and actual treatment 
variables (energy/spot), time for entire procedure, procedure variations (e.g., SAWSR 
remounting), and drug treatment before, during and after procedure. 
8.4.8 Postoperative Care 
Postoperative instructions will be given to each subject and reviewed prior to discharge. 
The following postoperative eye drops will be prescribed for the following minimum 
times: 
1. 
Prolensa 1 drop immediately after the primary treatment, then 1 drop in 
the treated eye at bedtime on the day of the treatment and the following 
morning (3 drops total). 
2. 
Preservative-free artificial tears PRN (e.g. Blink Tears sterile, single-use) 
All postoperative eye drop usage will be recorded in the subject's chart.  Other 
prescription or nonprescription medications, including pain medications and medically 
indicated ophthalmic medications, may be taken as needed throughout the study. Use of 
any ophthalmic drops containing benzalkonium chloride is not recommended during the 
first week after the treatment. 
 
8.5 
Follow-Up Visits (1 Day, 1 Week, 1, 3, 6, 9, 12 and 24 months) 
A study flow chart summarizing the follow-up examination schedule and required 
procedures to be performed at each study visit is provided in Appendix A. All subjects 
will be seen at 1 day, 1 week and 1, 3, 6, 9, 12, 18 and 24 months after the Opti-K™  
treatment. All final exam procedures will be completed at the 24-month visit. If subject 
drops out or is withdrawn from the study before completing the Month 24 examination, 
the Month 24 procedures should be performed as the Final Exam whenever possible. If a 
final examination cannot be performed, the last scheduled examination completed by the 
subject will be considered the final examination.  
 
The following procedures will be performed at each visit unless noted otherwise.  
• Documentation of interim medical, ocular, and medication histories since 
previous visit 

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§ UCVA distance 
§ UCVA near 
§ BSCVA distance  
§ BSCVA near 
§ Binocular UCVA distance 
§ Binocular UCVA near 
§ Contrast sensitivity (Months 1, 6, 12, and 24)2 
§ Mesopic pupil diameter (Months 1, 6, 12, and 24) 
§ Manifest refraction 
§ Cycloplegic refraction (Months 1, 6, 12, and 24) 
§ Keratometry (Months 1, 6, 12, and 24) 
§ Corneal topography 
§ Aberrometry (report as 6 mm, 8th order) with pupil dilated to at least 6.5 mm3 
§ Intraocular pressure (omit Day 1) 
§ Specular microscopy (Week 1 post-secondary treatment; Months 1, 3, 6, 12, 
and 24)3 
§ Pachymetry (Months 6, 12, and 24) 
§ Slit lamp examination of the cornea, anterior chamber and lens 
§ Dilated fundus exam (Months 6, 12, and 24) 
• NEI RQL-42  questionnaire (Months 1, 3, 6, 12, and 24) 
• Subjective complaint questionnaire (Months 1, 3, 6, 12, and 24) 
• Adverse events/complications 
• Other diagnostic tests (at investigator’s discretion) 
 
Topography, manifest refraction, and visual acuities should be done before dilation and 
the before the completion of the cycloplegic refraction and any other potential tear 
disruptions tests (e.g., IOP measurement) so that the tear film is not altered. Aberrometry 
should be performed after dilation and before applanation tonometry. 
 
Other optional diagnostic tests may be performed at the investigator’s discretion (e.g., 
corneal hysteresis, OCT, topography and wavefront measurements with other devices 
such as the Oculyzer and iTrace) to further evaluate the subject’s postoperative outcome. 
Optional diagnostic tests should be performed after the examination requirements of the 
study have been completed. The results of optional diagnostic tests will not be recorded 
on the case report forms. 
 
Reasonable effort will be made by telephone and mail to contact subjects who miss a 
scheduled follow-up visit. 
 
Any observations of known optimal keratoplasty postoperative events will be 
documented in the subject’s medical records and evaluated by the investigator and the 
sponsor to determine whether it is a reportable event. 
                                               
2 Contrast sensitivity and specular microscopy are performed as substudies at a single clinic. 
3 Pupils should be dilated pharmacologically using a short-acting mydriatic  or cycloplegic agent, such as 
phenylephrine or tropicamide (Mydriacyl).. 

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8.6 
Retreatment  
No retreatments will be performed during the study.  
8.7 
Safety Monitoring 
Subjects will be observed closely to detect any adverse events or complications that may 
have occurred.  On the day of treatment and at each follow-up visit, a non-leading 
question, such as “How are you seeing?,” may be used to determine whether any 
complications or adverse events might have occurred since the last visit.  The presence or 
absence of adverse events or complications will be documented. 
 
Ophthalmic safety will be evaluated by slit lamp examination of the operated eye, 
measurement of refraction, and measurement of visual acuity.  In the case of an adverse 
event or complication, these tests, and any others deemed necessary, may be repeated 
before the next scheduled visit at the investigator’s discretion.  Appropriate supportive 
and/or definitive therapy may be administered as required. Any complications or adverse 
events will be recorded in the medical record/case report form. 
 
8.8 
Post-Study Procedures 
Subjects will be discharged from the study after the final examination is complete.   
8.9 
Device  Accountability 
All use of the Opti-K™  System will be under the direct supervision of the principal 
investigator or his designee. 
8.10 Early Withdrawal from Study 
Subjects will be advised that they are free to withdraw from the study at any time.  The 
investigator may discontinue a subject if a serious adverse event occurs and it is in the 
subject's best interest not to continue in the study or if the subject moves and the subject 
cannot complete the remainder of the follow-up visits. When a subject withdraws early 
from the study, a final examination will be performed at the time of withdrawal if 
possible. 
 
 
9.0 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
A detailed statistical analysis plan (SAP) will be developed for analysis of all data for this 
study.  Required analyses and target endpoints that will be included in this SAP are 
summarized below.  The methods by which each of these analyses is performed will be 
included in the SAP.  The required analyses and target endpoints include, but are not 
limited to those listed below. 
 
Tabulation of summary statistics, graphical presentations, and statistical analyses will be 
performed using SAS
® software.  All subjects who are enrolled in this study will be 
included in the safety analysis.  All two sided testing and confidence intervals will use a 
significance level of 5%.  
 

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9.1 
Sample Size 
In the initial (feasibility) clinical study, 40 sighted patients will be treated unilaterally in 
their dominant eyes.  Following demonstration of safety and effectiveness in initial 
clinical study sighted eyes (based on an initial treatment nomogram – see Table 8.3.2-1), 
the treatment nomogram will be refined and used in an expanded study.  
 
After expansion, it is estimated that at least 300 patient eyes will be treated in the full 
study.  This sample size is based on the expected observation of zero subjects with a 
serious adverse event such that the upper one-sided 95% confidence limit is less than 
1.0%. With 300 eyes, the upper one-sided exact confidence limit is 1.0 %.  The 
computation for the number of eyes n is taken from application of the exact binomial 
distribution:  
(
) (
)
05
.0
01
.0
1
01
.0
0
0
<
−
⎟⎟
⎠
⎞
⎜⎜
⎝
⎛
n
n
 
which reduces to: 
(1-0.01)n < 0.05 
which is solved by taking logarithms of both sides: 
n log(0.99) < log (0.05) 
so n > [log (0.05)/log (0.99)] or n > 298.0725 which was rounded up to 300. 
For effectiveness, the proportion of eyes with an improvement of 2 or more lines of D-
UCVA at 12 months post-treatment will be reported.  The hypothesis is that the 
proportion of eyes that achieve a minimum of 2 lines improvement over baseline at 12 
months after treatment will be greater than 85%.  In statistical terms, the hypothesis is 
written as:   
H0: Pt ≤ 0.85 
versus 
Ha: Pt > 0.85 
where Pt is the proportion of eyes with at least a 2-line improvement in D-UCVA.  Early 
results from a clinical study outside the United States indicate that the expected 
proportion of eyes that achieve 2 or more lines improvement in D-UCVA is 
approximately 90%.  With 300 eyes, the power is 80.9% to detect a statistically significant 
improvement in D-UCVA above 85% with a one-sided exact binomial test with alpha of 
0.05. 
 
The sample size is increased to account for a potential 10% non-completion rate.  Thus 
the number of eyes that need to be recruited is 300/0.9 = 333.  Rounding upwards, up to 
350 eyes will need to be enrolled in the pivotal arm of the trial to assess the primary 
endpoints. 
 
Study Populations 
There are two study populations identified in the study.  The first is the completed cases 
(CC) population that includes those patients who complete the study through one year of 

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follow-up.  The second is the intent to treat (ITT) population that includes all patients 
who enter the study and are treated with the laser.  The primary safety analysis will be 
done on the ITT population and the primary effectiveness analysis will be done on the 
ITT followed by a confirmatory analysis in the CC population.   
 
9.2 
Analysis by Indication 
All eyes enrolled in the study are being treated for hyperopia with the treatment target of 
emmetropia. Thus, no analysis by indication will be performed. 
9.3 
Accountability 
Accountability by postoperative visit will be calculated as illustrated in Table 9.3-1 
below. 
 

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Table 9.3-1: Accountability by Postoperative Visit 
 
1 Month 
3 Months 
Available for Analysis2 
n/N1(%)  
 
 
Missed Visit3 
n/N1 (%) 
 
 
Discontinued4 
n/N1 (%) 
 
 
Active5 
n/N1 (%) 
 
 
Lost to follow-up6 
n/N1 (%) 
 
 
% Accountability = Available for Analysis 
(Enrolled - Discontinued - Active) 
 
 
Where,  
1 
Enrolled (N) = total number of subject eyes enrolled in the study.  
2  
Available for analysis = total number of eyes for whom data are available at each 
postoperative interval.  
3  
Missed visit = total number of eyes that missed the visit, but were otherwise accounted 
for. Includes those eyes that missed the visit but were seen at a later visit. 
4  
Discontinued = total number of eyes that discontinued follow-up prior to completion of 
the study for any reason (e.g., retreatment, moved away).  
5  
Active (not yet eligible for the interval) = total number of eyes that have not yet reached 
the visit interval.  
6  
Lost to follow-up = total number of eyes for whom a visit at the prescribed visit or later 
was not completed and who are not considered to be active or discontinued. 
 
9.4 
Screening 
The screening data for all subjects who are screened but do not meet eligibility criteria 
will not be analyzed or tabulated nor collected on the case report forms. 
 
9.5 
Subject Characteristics 
The number of subjects included in the safety and/or effectiveness evaluations, subjects 
completing the study, and the reasons for any withdrawals will be tabulated by counts 
and percents.  Continuous demographic data will be summarized using descriptive 
statistics.  Categorical demographic data will be summarized using counts and percents.   
Abnormal medical histories, ocular histories, and prior/concurrent medications obtained 
on the screening visit will be presented in data line listings. 
9.6 
Primary Efficacy Criteria 
• The following effectiveness endpoints and target values will be addressed at all 
post-treatment examinations for all treated eyes: 
• E1. The proportion of eyes (target: at least 85%) that achieve successful distance 
uncorrected visual acuity (D-UCVA) improvement defined as 2 lines (10 letters) 
or more improvement in D-UCVA following Treatment will be reported. 

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• E2.  The proportion of eyes (target: at least 85%) that achieve distance 
uncorrected visual acuity (D-UCVA) of 20/40 or better following Treatment and 
the proportion of eyes that achieve D-UCVA of 20/40 or better following 
Treatment as a function of the pre-Treatment D-UCVA will both be reported. 
• E3. The proportion of eyes that achieve predictability (achieved versus attempted) 
of distance uncorrected visual acuity (D-UCVA) within ± 2 lines (target: at least 
85%) and within ± 1 line (target: at least 50%) of the intended value (20/20) at the 
point at which stability is first reached will be reported. 
• E4.  The percentage of eyes that achieve predictability (achieved versus 
attempted) of manifest refraction, spherical equivalent (MRSE) within ± 1.0 D 
(target: at least 75%) and within ± 0.5 D (target: at least 50%) of the intended 
value (0.0 D) will be reported based on aberrometry readings. 
• E5.  In an expanded clinical study, after the treatment nomogram has been 
refined, the percentage of eyes that achieve stability (as defined below) will be 
reported; means ± standard deviations of MRSE will also be reported for pre-
Treatment as well as post-Treatment exams. 
• Stability analyses, to be performed for the time intervals between all consecutive 
pairs of scheduled postoperative refractions, are: 
1. A – Percentage of eyes that achieve: 
§ A1 – a change of less than or equal to 1.00 D of MRSE between 
two refractions performed at 1 month and 3 months, and between 
subsequent refractions performed at least 3 months apart; 
§ A2 – a change of less than or equal to 0.50 D of MRSE between 
two refractions performed at 1 month and 3 months, and between 
subsequent refractions performed at least 3 months apart; 
§ B – Mean overall change and change per month in MRSE between 
consecutive scheduled visits as determined by a paired analysis; 
§ C – Mean ± SD MRSE for the preoperative and each postoperative 
visit; 
§ D – Assessment of cylinder stability for correction of 
spherocylindrical refractive errors. 
• Note: refractive stability is generally accepted to have been 
achieved at the latter of two postoperative refractions 
performed at least 3 months apart or at 3 months after 
surgery when compared to the 1-month interval, if all the 
following recommended criteria are met: 
o α – At least 95% of the treated eyes have a change 
of ≤ 1.00 D of MRSE between the two refractions; 
o β – The mean rate of change of MRSE, as 
determined by a paired analysis, is ≤ 0.5 D per year 
(0.04 D/month) over the same time period; 
o γ – The mean rate of change of MRSE decreases 
monotonically over time, with a projected 
asymptote of zero or a rate of change attributable to 
normal aging; 

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o δ – The 95% confidence interval for the mean rate 
of change includes zero or a rate of change 
attributable to normal aging; and 
o ε – Stability is confirmed at least 3 months after the 
stability timepoint by a statistically adequate 
subgroup. 
• E6. In an expanded clinical study, after the treatment nomogram has been refined, 
the proportion of eyes that achieve improvements (as well as reductions or 
unchanged values) of questionnaire items listed in the National Eye Institute – 
Refractive Error Quality of Life (NEI-RQL) instrument (see Appendix V) will be 
reported. 
 
All of the above effectiveness measures will be reported for all treated eyes. 
 
9.8 
Clinical Safety Endpoint Criteria 
The primary safety endpoint is the proportion of eyes with the occurrence of serious 
adverse events defined in the list below: 
 
Serious Adverse Events 
1.  Corneal infiltrate or ulcer 
2.  Persistent central corneal epithelial defect at 1month or later post-Treatment 
3.  Corneal edema at later than 1month post-Treatment 
4.  Corneal perforation 
5.  Uncontrolled intraocular pressure (IOP) with increase of >5 mm Hg above 
baseline, and any IOP above 25 mm Hg  
6.  More than 10% endothelial cell loss as measured by specular microscopy at 6 
months or later post-Treatment 
7.  Retinal detachment 
8.  Retinal vascular accidents 
9.  Decrease in BSCVA of greater 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 
10. Any other vision-threatening event 
The hypothesis is that the rate of serious adverse events defined above is less than 1.0% 
per type and less than 5.0% in toto.  Rates of occurrence of each of these serious adverse 
events, together with the incidence of adverse events in toto, will be reported. 
 
Other safety endpoints include: loss of 2 or more lines of D-BSCVA, D-BSCVA worse 
than 20/40 and induced manifest refractive astigmatism of > 2.0 D. 
9.8.1 Adverse Events and Complications 
All subject questionnaire data, complications, and adverse events will be tabulated and 
summarized. 
 

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9.8.2  Key Safety Parameters 
The following safety endpoints and target values will be tabulated and reported at all 
post-treatment examinations for all treated eyes: 
o S1. Less than 5.0% of patients should lose more than 2 lines of distance best 
spectacle-corrected visual acuity (D-BSCVA). 
o S2.  Less than 1.0% of patients should have D-BSCVA worse than 20/40. 
o S3.  Less than 5.0% of patients should have induced manifest refractive 
astigmatism of    >2.0 D. 
o S4.  Less than 1.0% of patients should experience each type of serious adverse 
event and less than 5.0% of patients should experience serious adverse events in 
toto. 
 
The following additional safety endpoints and target values will be tabulated and reported 
at each measurement timepoint: 
o S5.  Less than 1.0% of eyes should lose more than 10% of central or peripheral 
endothelial cell density (ECD). 
o S6.  Less than 1.0% of eyes should lose more than 0.3 log units of contrast 
sensitivity. 
 
9.9 
Other Outcome Measures 
Intraocular pressure will be tabulated by counts and percents.  Other outcome measures, 
such as pupil size, central pachymetry, slit lamp examinations, and dilated fundus 
examinations will be reported in data line listings. 
 
9.10 NEI-RQL-42 
The parameter evaluated will be the difference in the numeric score for the NEI-RQL-42 
administered post treatment at the time point of stability to the pre-treatment or baseline 
composite score.  The NEI-RQL-42 will be administered pre-treatment at screening to 
establish the subject’s baseline and at all post operative time points after the primary 
treatment starting at 1 Month. It is believed that by the timepoint of refractive stability the 
positive effect of the surgery will have manifested itself in the visual function quality 
assessment.   
 
Scoring will be calculated according the NEI-RQL-42 Scoring Manual.4  Scoring the 
RQL-42 is a two-step process: 
 
1. Numeric Score:  Original numeric values from the survey are recoded following 
the scoring rules outlined in Table 1. All items are scored so that a high score 
                                               
4 Hays, R. D., & Spritzer, K. L. (2002, February). National Eye Institute 
Refractive Error Quality of Life Instrument (NEI-RQL-42™), Version 1.0: A 
Manual for Use and Scoring. Los Angeles, CA. 
 

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represents better quality of life. Each item is then converted to a 0 to 100 possible 
range so that the lowest and highest possible scores are set at 0 and 100, 
respectively. In this format, scores represent the achieved percentage of the total 
possible score. For example, a score of  50 represents 50% of the highest possible 
score. 
 
2. Scale Scores:  Items within each scale are averaged together to create the 13 scale 
scores. Table 2 indicates which items contribute to each scale. Scales with at least 
one item answered can be used to generate a scale score. Items that are left blank 
(missing data) are not taken into account when calculating the scale scores. Scores 
represent the average for all items in the scale that the respondent answered. 
Scales included in the scale score analysis are: 
 
o Clarity of vision  
o Expectations  
o Near vision  
o Far vision  
o Diurnal fluctuations  
o Activity limitations  
o Glare  
o Symptoms 2b 
o Dependence on correction 16 
o Worry  
o Suboptimal correction 2 
o Appearance  
o Satisfaction with correction  
 
It is desired to determine whether the mean responses from a population at two different 
time points are equal to each other; therefore, the hypotheses to be tested are: 
H0:µD = 0 versus HA:µD  ≠ 0  
where µD is the mean difference in the numeric score between the two time points.   
 
If it is assumed that the data from both time points are normally distributed, then the test 
statistic for testing the above hypothesis is a t-test.  That is, the null hypothesis is rejected 
if t>t(df,1-α/2), where 
n
s
X
t
D
D
2
)
0
(
−
=
 
Published literature indicates that a difference of 6 points or more on the composite 
scores is a clinically significant change.5 
 
                                               
5 Schein OD, Vitale S, Cassard SD, Steinberg EP. Patient outcomes of refractive surgery: The refractive status and 
vision profile. J Cataract Refract Surg. 2001 May;27(5):665-73. 

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9.11 Subjective Symptom Questionnaire 
The subjective symptoms patient questionnaire will be administered pre-treatment at the 
time of the screening examination or on the day of treatment to establish the subject’s 
baseline and at all post operative time points starting at 1 month.  The presence of each 
subjective symptom is rated on a 5-point scale that corresponds to:  None (1), Mild (2), 
Moderate (3), Marked (4), Severe (5).  Symptoms that are evaluated are:  light sensitivity, 
difficulty driving at night, reading difficulty, double vision, fluctuation in vision, glare, 
halos, starbursts, dryness, pain, foreign body sensation, and other. Questions that evaluate 
patient satisfaction and patient willingness to have the procedure again will also be 
included on the questionnaire. 
 
Severity ratings will be tabulated by counts and percents for each symptom for each 
postoperative visit, beginning at 1 month.  Descriptive statistics will be presented for the 
changes in the degree of severity of patient symptoms compared to the baseline pre-
treatment severity rating for the cohort at 6 months.  The improvement in subjective 
complaints will be analyzed, as determined by the difference in the percentage of patients 
who have marked/severe ratings of each symptom at 6 months compared to the 
percentage who have marked/severe ratings of each symptom at baseline. For each time 
point of evaluation, descriptive statistics will be presented for the entire cohort. 
 
9.12 Retreatments 
Retreatments cannot be performed in the study.  
 
9.13 Dropouts/Lost-to-Follow-up 
Subjects may drop out at any time during the study.  Effectiveness data from dropouts 
will be included through the last recorded subject visit, except in those instances where 
missing data precludes the analysis of serial or comparative data points.  All treated 
subjects/eyes will be included in the safety analysis 
 
9.14 Poolability 
The demographic data for all sites will be tested for homogeneity.  This will include age, 
gender, and race.  Also, the key baseline and final efficacy endpoints will be tested for 
differences among the sites.  For baseline, the MRSE will be evaluated for differences 
among sites and for final efficacy, refractive predictability will be assessed for 
differences amongst the sites.  Continuous variables will be assessed via ANOVA and 
categorical variables (sex and race) will be assessed using Fisher’s exact test. 
 
9.15 Missing data 
To assess the impact of missing data, a sensitivity analysis will be conducted.  Under this 
analysis, the primary endpoints will be assessed in a worst case and best case scenario.  
For this study, the best case scenario is to use the last observation carried forward and the 
worst case is to use the baseline value.  Since the number of missing data points in this 

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type of study has been extremely small, it is anticipated that the sensitivity analysis will 
yield results similar to the main analysis. 
 
 
10.0 ETHICAL AND REGULATORY CONSIDERATIONS 
This study will be conducted in accordance with FDA’s Good Clinical Practice 
regulations.  
10.1 Informed Consent 
In accordance with the provision of 21 CFR Part 50, each subject will provide written 
informed consent for participation in this study prior to the use of the investigational 
device (Appendix B).   
 
The study will be explained to the prospective subject by the investigator or his designee.  
The nature of the experimental product will be explained together with potential hazards 
of the surgical procedure, including any possible adverse reactions.  The subject will be 
informed that he/she is free to terminate participation in the study for any reason.  One 
copy of the signed consent form will be retained in the medical record.  
10.2 Institutional Review Board 
This protocol and the informed consent form will be approved initially and reviewed 
annually by an Institutional Review Board (IRB) constituted according to FDA 
regulations   Progress reports will be submitted at the completion of the study or at least 
once yearly, whichever comes first, to the IRB.  Serious adverse events will be reported 
to the IRB and the FDA in accordance with applicable FDA regulations for serious 
adverse events. 
10.3 Complications and Adverse Events 
Throughout the course of the study, every effort will be made to remain alert to possible 
adverse events and complications.  If adverse events occur, the first concern will be the 
safety of the patient.  Appropriate medical intervention will be made.  Any adverse event 
observed by the investigator or reported by the patient, regardless of severity and whether 
or not ascribed to the study materials, will be recorded in the appropriate section of the 
patient's data collection forms. 
Serious adverse events will be documented until their medical outcome is stable and 
written reports will be provided to the Sponsor by the Investigator.  The patient will be 
continued in the study until protocol visits are completed. 
Serious and/or potentially vision-threatening adverse events include, but are not limited 
to, the following:  
o Corneal infiltrate or ulcer,  
o Persistent central corneal epithelial defect at 1 month or later post-treatment,  
o Corneal edema at later than 1 month post-treatment, 
o recurrent corneal erosion at 1m or later post-Treatment, 
o corneal perforation, 
o retinal detachment, 

CONFIDENTIAL 
o retinal vascular accident, 
o uncontrolled intraocular pressure (IOP) with increase of >5 mm Hg above 
baseline, and any IOP above 25 mm Hg, 
o more than 10% endothelial cell loss as measured by specular microscopy at 3 
months or later post-Treatment, 
o decrease in BSCVA of greater 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, and any other vision-threatening event. 
Complications include, but are not limited to, the following: 
o Corneal edema between 1 week and 1 month post-Treatment, 
o Persistent peripheral corneal epithelial defect at 1 month or later post-Treatment,  
o Keratitis (non-vision threatening), 
o Conjunctivitis, and 
o Pain, tearing, photophobia and/or foreign body sensation at 1 month or later post-
Treatment. 
All clinical findings (both serious adverse events and complications) are to be reported on 
Case Report Forms (CRFs).  Complications should be reported on each CRF with clinical 
grading using a scale of Trace, Mild, Moderate or Severe to assess grade. Each of these 
grade scales is defined on the CRFs.  Opacities in treatment spots should be individually 
graded on a scale of 1 to 4 (none, trace, mild, dense) and their depths graded on a scale of 
1 to 4 (≤ 25%, 26 to 50%, 51 to 75%, ≥ 76% ). Anterior chamber observations should be 
described and graded as indicated on each CRF.  
 
Complications will be reported in routine reports to FDA and the IRB but individual 
reports are not required. 
10.3.1 Serious and Unanticipated Adverse Device Effects 
An unanticipated adverse device effect is defined as “any serious adverse effect on health 
or safety or any life-threatening problem or death caused by, or associated with, a device 
if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan, or any other unanticipated serious 
problem associated with a device that relates to the rights, safety or welfare of subjects.” 
 
10.3.1.1 Sponsor Responsibilities  
In accordance with 21 CFR Part 812.150(a)(1) and (b)(1), the sponsor shall promptly 
report the results of an evaluation of any serious and unanticipated adverse device effect 
to FDA, all reviewing IRB’s and participating investigators (if any) as soon as possible, 
but not later than 10 working days after the sponsor first receives notice of the effect.  
Thereafter, the sponsor shall submit such additional reports concerning the effect as the 
FDA requests. Complications and non-serious or anticipated adverse events should be 
documented and tabulated but need not be submitted by the sponsor to the FDA as 
individual reports. All vision threatening adverse events should also be reported to FDA, 
all reviewing IRB’s, and all participating investigators in the same manner as reporting a 
serious and unanticipated adverse device effect. 
 

CONFIDENTIAL 
10.3.1.2 Investigator Responsibilities 
Investigators should report all serious and unanticipated and all vision threatening 
adverse events to the sponsor within 10 working days of first learning of the event. Those 
that are determined to be serious and unanticipated after sponsor review should also be 
reported the IRB within 10 working days of first learning of the event. Should the IRB 
have more stringent time requirements, the reporting requirements of the IRB will be 
followed.  
 
10.3.2 Non-serious or Anticipated Adverse Events 
Non-serious or anticipated adverse events and complications should be documented on 
the case report forms and tabulated for reporting but need not be submitted as individual 
reports by the investigator to the sponsor or IRB. Should the IRB have different reporting 
requirements, the requirements of the IRB will be followed. 
 
10.4 Monitoring 
A monitor will be designated by the sponsor to oversee the progress of the investigation.  
The monitor may be an employee of the sponsor or a consultant to the sponsor.  The 
monitor will meet with the investigator and staff before the study, during the study, and at 
other appropriate times to ensure compliance with the FDA’s Good Clinical Practice 
requirements and with the protocol specifications.  All records pertaining to the study will 
be made available to the monitor at each review. 
 
10.5 Source Documents / Case Report Forms 
Adequate records will be maintained for the study including subject medical and surgical 
records, signed informed consent forms, and device use records.  All original source 
documentation will remain at the investigative site. Study data that are stored at the 
investigator site in any electronic medical records system, including measurements that 
are obtained electronically (e.g., topography), will be printed and retained in the study 
files. 
 
All study data will be recorded onto case report forms (electronic or paper) designed for 
the study. If paper case report forms are used, copies of the case report forms will be 
retained with the investigator’s study files and the original forms will be filed with the 
sponsor. 
 
10.6 Deviation from the Protocol 
The investigator will not deviate from the protocol without prior IRB and sponsor 
approval, unless such deviation is necessary to manage a medical emergency. The 
investigator will notify the IRB and the sponsor of any protocol deviation to protect the 
life or physical well-being of a subject in an emergency.  Such notice shall be given as 
soon as possible, but in no event any later than 5 working days after the emergency 
occurred.   All other revisions and/or amendments to the protocol that affect subject 

CONFIDENTIAL 
treatment, study outcome, or subject safety should be submitted in writing to the IRB and 
the sponsor for approval prior to implementation if the changes or deviations to the 
protocol affect the scientific soundness of the study or the rights, safety, or welfare of 
human subjects.  In this case, the change should not be implemented until IRB and 
sponsor approvals are obtained.  The investigator should maintain a record of all protocol 
deviations showing the dates of, and the reason for, each protocol deviation. 
 
Changes that affect the scientific soundness of the study or the rights, safety, or welfare 
of human subjects may also require FDA approval, in addition to sponsor and IRB 
approval, prior to implementation.  The sponsor and investigator will obtain such 
approvals, if required.  

CONFIDENTIAL 
APPENDIX A:  STUDY FLOW CHART AND EXAMINATION 
SCHEDULE 
 
 
Examination and/or 
Information 
Screen 
Tx 
1D 
1W 
1M 
3M 
6M 
9M 
12M 
18M 
24M6 
Demographics 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ocular, Medical & 
Medication History7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Opti-K™  Treatment 
 
X 
 
 
 
 
 
 
 
 
 
Distance and near UCVA8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Distance and near BSCVA9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Binocular D- and N-UCVA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Contrast sensitivity10 
X 
 
 
 
X 
 
X 
 
X 
 
X 
Pupil diameter11 
X 
 
 
 
X 
 
X 
 
X 
 
X 
Manifest refraction12 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cycloplegic refraction13 
X 
 
 
 
 
 
X 
 
X 
 
X 
Keratometry14 
X 
 
 
 
X 
 
X 
 
X 
 
X 
                                               
6 The 24 Month examination is the final examination for the study. If the study is terminated early or a patient is 
withdrawn from the study before completion of the 24 Month examination, the 24 Month procedures should be 
completed as a Final Examination, whenever possible. 
7 Ocular history should include history of contact lens wear. Non-specific questioning should be used at each visit to 
determine other vision-related complaints, complications, or adverse events that are not otherwise captured on the case 
report forms. Medication history should include all prescribed medications and any non-prescription medications taken 
on a daily basis. 
8
Distance and near visual acuity charts, chart luminance, ambient illumination, testing distances and testing procedures 
will be standardized for all clinical sites and investigators. For distance visual acuity measurements, Early Treatment of 
Diabetic Retinopathy Study (ETDRS logMAR) charts will be used at 4 meters optical distance, with chart background 
luminance in the range of 80 to160 cd/m², chart contrast 85% or greater, ambient illumination from dim to dark to 
maximize pupil size and with no surface within the patient’s field-of-view that exceeds the chart’s background in 
luminance.  Testing will be done by counting correct letters read; reporting will be in both decimal and Snellen 
notations. For near visual acuity measurements, ETDRS-style near visual acuity charts will be used at 40 cm distance, 
with chart background luminance, chart contrast, ambient illumination, other surface luminance, testing and reporting 
the same as for distance visual acuity measurements listed above. 
9 BSCVA should be performed using an ETDRS eye chart and recording the total number of letters that are seen. If 
visual acuity with spectacle correction is > 2 lines below that obtained preoperatively at 3 months or later, a hard 
contact lens over refraction should be performed to determine the effect of higher order aberrations and to estimate the 
best possible corrected visual acuity.  
10 Contrast sensitivity with and without glare should be performed using the Functional Vision Analyzer according to 
the contrast sensitivity testing protocol. Contrast sensitivity testing may be performed at other times at the investigators 
discretion to assess contrast related adverse events, complications, or complaints. The contrast sensitivity substudy will 
be completed at one clinical site with an enrollment of 68 eyes (assuming a 10% loss to follow-up; more eyes will be 
enrolled if necessary so that the completed cases cohort comprises at least 61 eyes) as recommended in Section E.3.1 of 
ANSI Z80.11. 
11 Pupil size should be assessed under dim conditions at the preop exam and final exam. Mesopic pupil size should be 
measured at all contrast sensitivity testing visits under the same lighting conditions used to perform the contrast 
sensitivity testing. Pupil size may be measured using a pupillometer (e.g. NeurOptics; San Clemente, CA) that can be 
operated under mesopic lighting conditions. 
12 Manifest refractions may be recorded on the source documents in the investigator’s usual notation (plus or minus 
cylinder format) and will be recorded onto the case report forms using the standard notation designated by the sponsor. 
13 One drop of 0.5% cyclopentolate HCl ophthalmic solution will be instilled into each eye for cycloplegia 
14 Keratometry data will be obtained using Simulated Keratometry outputs from corneal topography 

CONFIDENTIAL 
Examination and/or 
Information 
Screen 
Tx 
1D 
1W 
1M 
3M 
6M 
9M 
12M 
18M 
24M6 
Corneal topography15 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Aberrometry16 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Intraocular pressure17 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Specular microscopy18 
X 
 
 
 
X 
X 
X 
 
X 
 
X 
Pachymetry19 
X 
 
 
 
 
 
X 
 
X 
 
X 
Subjective questionnaire 
X 
 
 
 
X 
X 
X 
 
X 
 
X 
NEI RQL-42 questionnaire 
X 
 
 
 
X 
X 
X 
 
X 
 
X 
Slit-lamp exam20 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dilated fundus exam 
X 
 
 
 
 
 
X 
 
X 
 
X 
Adverse 
events/complications 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
                                               
15 Corneal topography measurements will be obtained using Orbscan II®, EyeSys® or equivalent instruments 
16 Aberrometry measurements will be obtained using a LADARWave CustomCornea Wavefront System (Alcon 
Laboratories, Irvine, CA). 
17 Intraocular pressure measurement by will be measured with a Goldmann tonometer or equivalent. 
18 A noncontact specular microscope (CellCheck XL, Konan Medical USA, Torrance, CA) will be used in a substudy 
on 40 eyes. Test conditions include use of images with at least 100 countable (i.e., not in shadow, washed out or 
blurred) cells grouped in a uniform area.  Images will be obtained centrally and at two peripheral locations (12 and 6 
o’clock at 3 mm from center).  Automated image analysis will be used to measure endothelial cell density (ECD). Post-
Tx vs. pre-Tx ECD will be used to calculate endothelial cell loss. 
19Pachymetry measurements of central corneal thickness will be obtained using an ultrasonic pachymeter, Pentacam, or 
Orbscan II®.  Optionally, additional pachymetry measurements of pericentral and peripheral corneal thickness will be 
obtained using an Orbscan II® system, Pentacam, or equivalent. 
20 Slit lamp will include a complete survey of the anterior segment, with detailed examination of the cornea and 
recording and grading of overall corneal clarity and any preoperative abnormalities. Post-treatment assessments will 
include the opacity (graded as absent, detectable, or moderately dense) of treated spots, together with the status of the 
corneal epithelium examined after instillation of sodium (Na) fluorescein and lissamine green B to visualize possible 
epithelial damage to cornea and/or conjunctiva.  
 

CONFIDENTIAL 
APPENDIX B:  CFR 50.25 - ELEMENTS OF INFORMED CONSENT 
 
BASIC ELEMENTS OF INFORMED CONSENT:  In seeking informed consent, the 
following information shall be provided to each subject. 
 
1. 
A statement that the study involves research, an explanation of the purpose of the 
research and the expected duration of the subject’s participation, a description of 
the procedures to be followed, and identification of any procedures which are 
experimental. 
2. 
A description of any reasonably foreseeable risks or discomforts to the subject. 
3. 
A description of any benefits to the subject or to others which may reasonably be 
 
expected from the research. 
4. 
A disclosure of appropriate alternative procedures or courses of treatment, if any,
 
that might be advantageous to the subject. 
5. 
A statement describing the extent, if any, to which confidentiality of records 
 
identifying the subject will be maintained and that notes the possibility that the 
 
U.S. Food and Drug Administration may inspect records. 
6. 
For research involving more than minimal risk, an explanation as to whether any 
 
compensation and an explanation as to whether any medical treatments are 
 
available if injury occurs and, if so, what they consist of, or where further 
 
information may be obtained. 
7. 
An explanation of whom to contact for answers to pertinent questions about the 
research and research subject’s rights, and whom to contact in the event of a 
research-related injury. 
8. 
A statement that participation is voluntary, that refusal to participate will involve 
no penalty or loss of benefits to which the subject is otherwise entitled, and that 
the subject may discontinue participation at any time without penalty or loss of 
benefits to which the subject is otherwise entitled. 

CONFIDENTIAL 
APPENDIX C: TEST METHODS 
 
Visual Acuity (VA) assessment – Distance and near visual acuity charts, chart 
luminance, ambient illumination, testing distances and testing procedures will be 
standardized for all clinical sites and investigators.   
For distance visual acuity measurements, Early Treatment of Diabetic Retinopathy Study 
(ETDRS logMAR) charts will be used at 4 meters optical distance, with chart background 
luminance in the range of 80 to160 cd/m², chart contrast 85% or greater, ambient 
illumination from dim to dark to maximize pupil size and with no surface within the 
patient’s field-of-view that exceeds the chart’s background in luminance.  Testing will be 
done by counting correct letters read on different eye charts for the two eyes and in a 
randomized testing order; reporting will be in both decimal and Snellen notations. The 
subject will be adequately masked by testing UDVA through a phoropter with a plano 
correction in the test eye and an occluder over the other eye.  The subject will be 
instructed to close his/her eyes while the occluder is being switched from one eye to the 
other. 
For near visual acuity measurements, ETDRS-style near visual acuity charts will be used 
at 40 cm distance, with chart background luminance, chart contrast, ambient illumination, 
other surface luminance, testing and reporting the same as for distance visual acuity 
measurements listed above.    
 
Contrast Sensitivity 
Contrast sensitivity will be evaluated in a substudy at one clinical site according to the 
manufacturer’s instructions using the Functional Vision Analyzer (StereoOptical; 
Chicago, IL). The Functional Vision Analyzer is a precision vision testing device that can 
be used as a clinical testing device or for research related to vision testing and clinical 
trials. The Functional Vision Analyzer’s precision illumination is continually controlled 
by a microprocessor for accuracy and repeatability of the tests. The exclusive LED (Light 
Emitting Diode) system allows complete homogenous illumination that eliminates hot 
spots on testing slides, which can create inaccuracies of test results. This instrument is 
designed to do quick, accurate, reliable and confidential testing. 
The instrument automatically monitors and calibrates the light level to 3.0 cd/m² for night 
or 85 cd/m² for day. It is equipped with the FACT™ sine-wave contrast sensitivity slide 
package. VSRC's patented Functional Acuity Contrast Test (FACT) Chart is an accurate 
and comprehensive sine-wave grating chart that tests functional visual acuity. Developed 
by Dr. Arthur Ginsburg, the FACT sine-wave grating chart tests five spatial frequencies 
(1.5, 3, 6, 12, and 18 cycles/degree) and nine levels of contrast. The luminance and 
gratings satisfy the ANSI IOL and laser standards for contrast sensitivity testing. The 
patient determines the last grating seen for each row (A, B, C, D and E) and reports the 
orientation of the grating: right, up or left. Results are recorded using EyeView Software 
or data collection sheets that are designed for use with the FACT charts. 
 
Contrast Sensitivity testing without Glare 

CONFIDENTIAL 
Dim the room lights to the level at which the test will be conducted. Do not turn on the 
contrast sensitivity testing apparatus until you are ready to perform the test.  Only the 
study eye is required to undergo contrast sensitivity testing. If both eyes are tested, the 
suggested test order is to first test the right eye, the left eye, then both eyes. The order of 
testing should be consistent throughout the study.  The recommended test strategy is as 
follows: 
o If the patient has come in from bright light conditions, allow the subject to dark 
adapt by having them sit for at least five minutes in the room where contrast 
sensitivity testing will be performed. 
o Complete photopic testing (85 cd/m2)  in the following order: 
o Photopic no glare (photopic 85 cd/m2) 
o Photopic with high glare (Level 2) 
o Allow the subject to dark adapt for approximately 5 minutes. 
o Complete mesopic testing (3 cd/m2)  in the following order: 
o Mesopic no glare 
o Mesopic with low and high glare (Levels 1 and 2 for the first 10 patients; 
either Level 1 or Level 2 will be used for additional patients)  
Always perform contrast sensitivity testing without glare prior to contrast sensitivity with 
glare testing.  
 
All subjects are to be tested with best spectacle-corrected visual acuity preoperatively and 
at 1 and 6 months after the treatment. At each testing session, contrast sensitivity will be 
measured for five spatial frequencies: 1.5, 3, 6, 12, and 18 cycles/degree (cpd). The 
subject will be asked to perform the test monocularly with the other eye completely 
occluded and in a dimly illuminated room. The subject will be asked to identify the sine-
wave gratings for each spatial frequency until he or she cannot recognize further patch 
gratings. The last patch grating that is observed will be recorded for each spatial 
frequency. 
 
Pupil Size (PS) measurement – Mesopic pupil size measurement will be completed 
using a pupillometer (NeurOptics, San Clemente, CA) operated under mesopic 
illumination conditions.  The substudy will be completed with the same patient cohort 
that receives contrast sensitivity evaluation. 
Manifest refraction and cycloplegic refraction will be obtained; one drop of 0.5% 
cyclopentolate HCl ophthalmic solution will be instilled into each eye for cycloplegia. 
Intraocular pressure (IOP) will be measured with a Goldmann tonometer or equivalent. 
Slit-lamp biomicroscopy will include a complete survey of the anterior segment, with 
detailed examination of the cornea and recording and grading of overall corneal clarity 
and any preoperative abnormalities. Post-Tx assessments will include the opacity (graded 
as absent, detectable, or moderately dense) of treated spots, together with the status of the 
corneal epithelium examined after instillation of sodium (Na) fluorescein and/or 
lissamine green B to visualize possible epithelial damage to cornea and/or conjunctiva.  
Pachymetry measurements of central corneal thickness will be obtained using an 
ultrasonic pachymeter.  Optionally, additional pachymetry measurements of pericentral 

CONFIDENTIAL 
and peripheral corneal thickness will be obtained using an Orbscan II® system or 
equivalent. 
Keratometry data will be obtained using Simulated Keratometry outputs from corneal 
topography - see below. 
Corneal topography measurements will be obtained using Orbscan II®, EyeSys® or 
equivalent instruments.   
Aberrometry measurements will be obtained using a LADARWave CustomCornea 
Wavefront System (Alcon Laboratories, Irvine, CA). 
Specular Microscopy (SM) assessment – A noncontact specular microscope (CellCheck 
XL, Konan Medical USA, Torrance, CA) will be used in a substudy on 40. Test 
conditions include use of images with at least 100 countable (i.e., not in shadow, washed 
out or blurred) cells grouped in a uniform area.  Images will be obtained centrally and at 
two peripheral locations (12 and 6 o’clock at 3 mm from center).  Automated image 
analysis will be used to measure endothelial cell density (ECD). Post-Tx vs. pre-Tx ECD 
will be used to calculate endothelial cell loss. 
Subjective questionnaires will be obtained using the National Eye Institute Refractive 
Error Quality of Life questionnaire (see Appendix V).  
All other examinations and test procedures will be conducted according to accepted 
ophthalmic examination standards.