A Prospective, Randomized Comparison of SMILE Surgery to Wavefront-guided LASIK Surgery
Phase: NA
Conditions: Myopia
Sponsor: Stanford University

 
A Prospective, Randomized Comparison of SMILE 
Surgery to Wavefront-guided LASIK Surgery   
NCT03067077 
October 6, 2020 
Edward Manche, Principal Investigator 
Stanford University 
Stanford, California 94305 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
The purpose of the study is to compare the results of wavefront- guided LASIK surgery 
to SMILE (small incision lenticule extraction) surgery in patients with nearsightedness 
with or without astigmatism. 
Objectives I hope to determine if there are any advantages/disadvantages of wavefront-
guided LASIK over SMILE surgery in nearsighted patients. We will be performing tests 
of visual performance to see if there are any advantages of one technology over the other. 
b. 
Rationale for Research in Humans 
We want to evaluate which of these surgical procedures produces superior results in 
humans. 
2. 
STUDY PROCEDURES 
a. 
Procedures 
The patients will have a comprehensive eye examination once they express an interest in 
the study. This is considered standard of care. This includes a slit lamp examination of 
the front of the eye and a dilated fundoscopic examination of the back of the eye. If there 
is any pathology noted that would exclude the patient from the study, then we will inform 
the patient and make an appropriate referral. if the patient is deemed appropriate for the 
study after a comprehensive examination included computerized videokeratography, then 
they can be enrolled. The patient will undergo bilateral simultaneous eye surgery. Which 
eye is treated with the WFG- LASIK and which eye is treated with SMILE will be 
randomized so there is a 50% chance for either eye to receive one treatment. The patients 
will be seen on the day of surgery, post op day one, one week, one month, three months, 
six months and one year. The patient will receive topical antibiotics in each eye for one 

October 6, 2020 
 
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week following the procedure. The patient will receive topical steroid ophthalmic drops 
for one week after treatment. The patient will also receive topical antibiotic ophthalmic 
drops for four days after treatment. All of this is within the usual and customary standard 
of care for the treatment of patients undergoing LASIK and SMILE surgery. 
 
The research aspect of the study is a comparison of outcomes between the two eyes. All 
of the procedures in the study are standard of care. 
b. 
Procedure Risks 
We are studying outcomes of WFG-LASIK and SMILE surgery. Both techniques are 
FDA approved and used in clinical practice. The research procedures are the least risky 
that can be performed consistent with sound research design. 
c. 
Use of Deception in the Study 
No deception will be used. 
d. 
Use of Audio and Video Recordings 
No audio or video recordings are planned for the study. 
e. 
Alternative Procedures or Courses of Treatment 
Alternative procedures include no surgery and continuing to wear glasses and contact 
lenses. Alternatives also include performing LASIK, SMILE or PRK surgery on both 
eyes outside of the study. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
The surgery is performed in both eyes at the same time. Once a patient has had a LASIK 
or SMILE surgery, there is no need to create an additional LASIK flap or SMILE 
surgery. Patients in both groups will receive the same postoperative care. 
g. 
Study Endpoint(s) 
We plan to follow the patients for one year. Patients may experience improvement in 
their vision 6-12 months following surgery so we will need to gather the full data to 
determine final outcomes. We will terminate the study prior to enrolling the projected 
participant population if we determine that one procedure is superior to the other. The 
study will end after 70 subjects have been enrolled. 
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
Most reports in the literature report comparable outcomes between SMILE surgery and 
WFG-LASIK surgery for similar levels of nearsightedness with and without astigmatism. 
b. 
Findings from Past Animal Experiments 
None. 

October 6, 2020 
 
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4. 
DEVICES USED IN THE STUDY 
a. 
IDE-Exempt Devices 
Investigational Device 1 
Name: 
Intralase IFS 
Manufacturer: 
Abbott Medical Optics, Inc. 
Investigational Device 2 
Name: 
AMO Visx CustomVue 
Description: 
Abbott Medical Optics, Inc. 
Investigational Device 3 
Name: 
VisuMax 
Description: 
Zeiss 
 
5. 
DRUGS, BIOLOGICS, REAGENTS, OR CHEMICALS USED IN THE STUDY 
a. 
Commercial Drugs, Biologics, Reagents, or Chemicals 
Commercial Product 1 
Name: 
Vigamox 
Dosage: 
Alcon Labs 
Manufacturer: 
QID x 1 week 
Commercial Product 2 
Name: 
Econopred 
Dosage: 
Alcon Labs 
Administration Route 
QID x 1 week 
Commercial Product 3 
Name: 
Proparacaine 
Dosage: 
Alcon 
Administration Route 
1 drop at time of surgery 
Commercial Product 3 
Name: 
Voltaren 
Dosage: 
Alcon 
Administration Route 
1 drop at time of surgery 
Commercial Product 3 
Name: 
Diazepam 
Dosage: 
Roche 
Administration Route 
5 mg at time of surgery 
Commercial Product 3 
Name: 
Vicodin 
Dosage: 
Generic 
Administration Route 
325 mg prn pain 
Commercial Product 3 
Name: 
Systane 
Dosage: 
Alcon 
Administration Route 
1 drop Q 4 hrs prn dryness 
6. 
DISINFECTION PROCEDURES FOR MEDICAL EQUIPMENT USED ON BOTH HUMANS AND 
ANIMALS 
None. 
 
 
 
 

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7. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
70 healthy subjects with myopia with and without astigmatism. These are the patients 
who typically seek out LASIK and/or PRK surgery to lessen or reduce their dependence 
on glasses and contact lenses. 
b. 
Age, Gender, and Ethnic Background 
Subjects age 22 and older with myopia with and without astigmatism will be eligible to 
participate. All genders and ethnic backgrounds are eligible to participate in the study. 
c. 
Vulnerable Populations 
N/A 
d. 
Rationale for Exclusion of Certain Populations 
Minors are not included because the lasers are not indicated for use in minors. 
Additionally, vision is not stable in minors. 
e. 
Stanford Populations 
Employees and students are eligible to participate in the study if they qualify. They will 
get the same written informed consent. 
f. 
Healthy Volunteers 
All subjects are healthy with myopia with and without astigmatism. We are studying 
outcomes of LASIK and SMILE surgery in healthy nearsighted eyes with and without 
astigmatism. 
g. 
Recruitment Details 
We plan to run advertisements in the local paper regarding the study. The patients will be 
informed of the details of the study on the telephone. 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
Subjects age 22 and older with healthy eyes. Nearsightedness between -1.00 diopters 
and -10.00 diopters. 
Subjects with less than or equal to 3.00 diopters of astigmatism. 
ii. 
Exclusion Criteria 
Subjects under the age of 22. 
Subjects with excessively thin corneas. 
Subjects with topographic evidence of keratoconus. 
Subjects with ectactic eye disorders. 
Subjects with autoimmune diseases. 
Subjects who are pregnant or nursing. 

October 6, 2020 
 
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Subjects must have similar levels of nearsightedness in each eye. They can not be 
more than 1.5 diopter of difference between eyes. 
Subjects with more than 3.00 diopters of astigmatism 
Subjects must have similar levels of astigmatism in each eye. They can not have 
more than 0.75 diopters of difference between eyes 
i. 
Screening Procedures 
j. 
We will attempt to screen patients on the telephone to determine if they are eligible. If 
they appear to be eligible on the telephone, then we will have them come in for a 
screening examination. Participation in Multiple Protocols 
We will ask subjects if they are participating in more than one study and this will be 
stated on the consent form. 
k. 
Payments to Participants 
There is no payment for participating in the study. The patients will receive a reduced fee 
of 
 per eye to participate in the study. 
l. 
Costs to Participants 
The patient is responsible for a fee of 
 per eye w/out discount and 
 per 
eye with the discount. 
m. 
Planned Duration of the Study 
The study is for one year. We estimate that the study will take approximately three years 
to complete. Total time per paticipant during the screening process is approximately 45 
minutes. Total time per participant for active participation in the study will be 
approximeately 10 to 12 hours. Total time per participant for analysis of the participant 
data is approximately 30 minutes. 
8. 
RISKS 
a. 
Potential Risks 
i. 
Investigational devices 
No investigational devices are to be used. The excimer laser(AMO Visx Star S4 
CustomVue) is FDA approved for use in LASIK surgery. The Intralase iFS 150 is FDA-
approved for used in LASIK surgery. The VisuMax is FDA approved for use in SMILE 
surgery. LASIK and SMILE surgery are performed in the excimer department. 
ii. 
Investigational drugs 
No investigational drugs are being used. 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
Vigamox - ocular irritation, stinging, allergy. 
Pred Forte - ocular irritation, increased intraocular pressure, cataract formation 
Systane - ocular irritation, burning, transient blurring of vision 

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Voltaren - ocular irritation, burning, allergy 
Proparacaine - ocular stinging, transient anesthesia of cornea 
Diazepam - nausea, drowsiness 
Vicodan - nausea, drowsiness 
iv. 
Procedures 
Corneal topography, slit lamp biomicroscopy, snellen visual acuity testing, low contrast 
visual acuity testing, and anterior segment ocular coherence tomography testing are all 
routine non-contact examinations performed in the ophthalmology clinic with essentially 
little or no risk. 
Applantation tonometry and pachymetry involve touching a probe to the eye to measure 
intraocular pressure and corneal thickness respectfully. There is a low risk of a corneal 
abrasion while performing these tests (less than 1%). These tests are routinely performed 
in all the patients seen in the excimer clinic. 
Corneal sensation measurement using Cochet-Bonnet aesthesiometry utilizes a nylon 
filament to stimulate the corneal nerves to measure corneal sensation. This device is 
commonly used in the clinic with essentially little or no risk. 
Fundus examination involves a dilated examination of the posterior pole of the eye. 
Bright light is projected into the eye. Patients can experience some discomfort secondary 
to the bright light. This test is also performed as a routine part of every comprehensive 
eye exam in the excimer clinic. 
 
The following are non-investigational procedures: 
LASIK 
Corneal topography 
Slit lamp biomicroscopy 
Fundus examination 
Pachymetry 
Applanation Tonomety 
Snellen visual acuity testing 
Low contrast visual acuity testing 
Anterior segment ocular coherence tomography 
Ultrasonic pachymetry 
Corneal sensation measurement using Cochet-Bonnet Aesthesiometry 
v. 
Radioisotopes/radiation-producing machines 
N/A 
vi. 
Physical well-being 
Low risk 
vii. 
Psychological well-being 
Low risk 
viii. 
Economic well-being 
Low risk 

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ix. 
Social well-being 
Low risk 
x. 
Overall evaluation of risk 
Low risk 
b. 
International Research Risk Procedures 
N/A 
c. 
Procedures to Minimize Risk 
We will perform regular examinations of subjects at frequent intervals. If any adverse 
effects are noted, the subject will receive the appropriate care as needed. Both eyes are 
being treated at the same time so we will be following patients after the treatment. 
d. 
Study Conclusion 
We expect the study to terminate after all subjects have been enrolled. We will terminate 
the study sooner if a clear advantage is seen with one procedure compared to the other. 
We may terminate the study earlier depending on our rate of enrollement. 
Individual subjects may be terminated for a variety or reasons including but not limited 
to: 
-failure to come to follow up visits 
-failure to follow the appropriate medication regimen 
-pregnancy 
-the subject needs to receive treatment not allowed in the study 
-the study is cancelled 
-unanticipated circumstances 
-other administrative reasons 
e. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 
All measures of visual performance including uncorrected visual acuity, best 
spectacle corrected visual acuity, low contrast visual acuity, higher order aberration 
analysis, anterior segment OCT imaging. 
ii. 
Person(s) responsible for Data and Safety Monitoring 
The principle investigator will be monitoring the data. 
iii. 
Frequency of DSMB meetings 
N/A 
iv. 
Reporting of Serious Adverse Events (SAEs), Suspected Unexpected Serious 
Adverse Reactions (SUSARs), or Unanticipated Problems (UPs) 
All adverse events will be reported to the IRB within one week of discovery. 

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v. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
Yes 
vi. 
Will a board, committee, or safety monitor be responsible for study monitoring? 
(Y/N) 
No 
f. 
Risks to Special Populations 
N/A 
9. 
BENEFITS 
Subjects should experience a reduction or elimination of their nearsightedness 
with or without astigmatism with a resultant improvement in their uncorrected 
visual acuity. We may discover that either SMILE surgery or WFG-LASIK surgery 
yields better results so future subjects can choose the better technology. 
10. 
PRIVACY AND CONFIDENTIALITY 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, Stanford 
Health Care, and Stanford Children’s Health.