Post Photorefractive Keratectomy (PRK) Use of an Eye Shield for Maintaining Vision and Mitigating Pain
Phase: NA
Conditions: Pain, Vision Nearsighted
Sponsor: Stanford University

 
 
 
 
Post Photorefractive Keratectomy (PRK) Use of an Eye Shield for 
Maintaining Vision and Mitigating Pain 
Study Protocol and Statistical Analysis Plan 
NCT01592643 
August 19, 2011 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 1 of 23 
V1 8/19/11 
Post Photorefractive Keratectomy (PRK) Use of an Eye Shield 
for Maintaining Vision and Mitigating Pain  
 
 
 
 
Protocol Number: CS 003.2 
 
August 19, 2011  
 
 
 
 
 
 
 
 
 
SUBMITTED BY:  
NEXIS VISION, INC 
191 JEFFERSON DRIVE  
MENLO PARK, 94025 
 
 
 
 
 
 
 
 
 
 
 
Protocol Reviewed and Approved by:  
XXXXXX 
 
 
 
_________________________________ 
__________________ 
Principal Investigator 
 
 
 
Date 
 
 
 
 
 
 
 
 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 2 of 23 
V1 8/19/11 
 
 
 
Table of Contents 
Introduction ............................................................................................................... 4 
Study Rationale ........................................................................................................ 5 
Materials ................................................................................................................... 5 
Risk Analysis ............................................................................................................ 5 
Study Objectives ....................................................................................................... 5 
Study Design ............................................................................................................... 5 
Selection of Study Population ................................................................................... 6 
Subject Inclusion Criteria .......................................................................................... 6 
Subject Exclusion Criteria ......................................................................................... 6 
Completion and Termination Criteria ........................................................................... 7 
Patient Withdrawal .................................................................................................... 7 
Study Procedures ........................................................................................................ 7 
Study Outcomes: ...................................................................................................... 7 
Study Treatment ....................................................................................................... 8 
Medications .............................................................................................................. 9 
Study Visits and Procedures ................................................................................... 12 
Screening ............................................................................................................... 12 
Visit 1 - Baseline ..................................................................................................... 12 
Visit 2 - Placement (0 hour) .................................................................................... 12 
Visit 3 - 1 hour Post-PRK ........................................................................................ 12 
Visit 4 – 1 day Post-PRK ........................................................................................ 13 
Visit 5 – 2 day Post-PRK ........................................................................................ 13 
Visit 6 – 3 days Post-PRK....................................................................................... 13 
Visit 7 – 4 days Post-PRK....................................................................................... 14 
Visit 10 – 1 week Post-PRK .................................................................................... 15 
Unscheduled Visits ................................................................................................. 16 
Study Completion ................................................................................................... 16 
Adverse Events ........................................................... Error! Bookmark not defined. 
Adverse Events and Reportable Adverse Events ................................................... 16 
Serious Adverse Events ......................................................................................... 17 
Unanticipated Adverse Material Effects .................................................................. 18 
Statistical Methods .................................................................................................... 18 
Ethical and Regulatory Considerations ..................................................................... 18 
Institutional Review ................................................................................................. 18 
Changes to the Study Protocol or Conduct of the Study ........................................ 19 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 3 of 23 
V1 8/19/11 
Patient Informed Consent ....................................................................................... 19 
Case Report Forms ................................................................................................ 19 
Study Material Information and Accountability ........................................................ 19 
Declaration of Helsinki ............................................................................................ 20 
Regulatory Requirements ....................................................................................... 20 
Anonymity ............................................................................................................... 20 
Monitoring ............................................................................................................... 20 
 
References ................................................................................................................ 22 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 4 of 23 
V1 8/19/11 
Introduction     
Laser in situ keratomileusis (LASIK) is the most popular form of refractive surgery worldwide.  
However, the LASIK procedure includes the creation of a corneal flap and involves a risk of both 
flap-related complications1 and corneal ectasia2.  Photorefractive keratectomy (PRK) is an older, 
well established, flapless refractive procedure that has been performed for over 20 years3.  
Unlike LASIK, eyes undergoing PRK incur no risk of flap-related complications and likely have a 
reduced risk of corneal ectasia compared to LASIK4-6.  Unfortunately, post-operative pain and 
delayed visual recovery remain substantial drawbacks for PRK compared to LASIK7.  Standard 
means for mitigating pain include the use of topical non-steroidal anti-inflammatory agents8, 
systemic pain-relief agents9 and the placement of a bandage contact lens10-11. Furthermore, this 
regimen does not address the visual deficit associated with the removal and subsequent re-
epithelialization of the cornea. While these measures are somewhat helpful, post-operative pain 
remains greater than that experienced with LASIK12 and visual recovery is significantly slower 
than LASIK. 
 
Although the primary reasons for post-PRK pain are not fully understood, one hypothesis is that 
corneal nerve fibers are exposed following epithelial debridement and stromal ablation during 
the first few post operative days until the epithelium heals13, and that even slight trauma to this 
area (i.e.- rubbing of eye lids against the wound) may cause severe pain.  This would explain 
why standard bandage contact lenses reduce pain somewhat but not completely, as they still 
freely move over the surface of the eye and may abrade the exposed nerve fibers.  Another 
observation is corneal swelling immediately after both PRK and LASIK. However, swelling is 
significantly reduced the day after surgery in LASIK whereas it increases in patients undergoing 
PRK. One reason for this may be the fact that the replaced LASIK flap following ablation limits 
hydration of the underlying tissue by preventing direct exposure of the ablated stromal tissue to 
the tear film. The current study is to evaluate an eye shield made of silicone with extremely high 
oxygen permeability and zero water content. The objective is to place the shield directly over the 
ablated stromal tissue in order to protect the cornea,  maintain normal corneal hydration 
avoiding edema,  and  promote wound healing. Furthermore, the silicone shield is designed not 
to move during blinking and eye movement providing for  the potential to significantly reduce 
pain and maintain vision following PRK.  
  

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 5 of 23 
V1 8/19/11 
 Study Rationale 
Although PRK is considered by many to be a safer refractive procedure than LASIK, the primary 
reason patients and doctors may be reluctant to choose PRK is the associated post operative 
pain and reduction in visual acuity. PRK is a very safe and well established refractive procedure, 
and an effective means of reducing pain and maintaining vision may allow it to be more widely 
adopted.  Covering the exposed PRK wound with a thin silicone shield has the potential to 
significantly reduce pain and maintain vision following PRK. 
 
Materials 
The materials used to make the corneal eye shield all have a history of use in medical devices 
such as IOL’s, contact lenses, and/or corneal shields. The shield materials used will include 
silicone and surface treatments designed to increase the wettability of the silicone.  The surface 
treatments will include well known plasma-deposited hydrocarbon coatings in sub-micron to 
micron thicknesses used in standard contact lens coating. 
All shields will be 300µm or less in center thickness tapering to the outer edge with an outer 
diameter ≤ 16mm. The shield will cover the cornea and part of the conjunctiva.  
 
Risk Analysis 
Silicone elastomer contact lenses are used to treat pediatric aphakia and also treat high myopia 
and keratoconus in children. 
 
Study Objectives 
Determine if silicone elastomer shields on the cornea following PRK can reduce pain and 
maintain vision associated with the epithelial defect during the initial post operative period 
following PRK. 
Study Design 
This will be a prospective clinical trial in which shields will be placed unilaterally or bilaterally in 
up to 100 healthy participants who have elected to undergo PRK to correct their refractive error. 
These patients will be evaluated over the course of 30 days following PRK while using the 
silicone shield.  The shield may be enhanced and its design altered as data is gathered through 
the study period.  
 
Principal Investigator 
XXXXXX 
 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 6 of 23 
V1 8/19/11 
 
 
Selection of Study Population 
Up to 100 patients who are candidates for PRK. 
 
Subject Inclusion Criteria 
Patients who meet the following entry criteria will be eligible for enrollment in this study: 
 
1. Patients scheduled to undergo bilateral PRK for correction of refractive error 
2. FDA approved treatment guidelines for PRK 
3. Age 18-60 
4. Epithelial defect created with a trephine ≤ 8.0 mm 
5. Patients able to understand the requirements of the study, willing to follow study 
instructions, provide written informed consent to participate, and comply with all study 
requirements, including the required study follow-up visits 
 
Subject Exclusion Criteria 
Excluded from the study will be individuals with the following characteristics: 
 
1. Any other anterior segment abnormality other than that associated with PRK 
2. Any abnormalities associated with the eye lids 
3. Uncontrolled blepharitis or dry eye 
4. Prior laser treatment of the retina 
5. Any ophthalmic surgery performed within three (3) months prior to study excluding PRK or 
LASIK 
6. Diagnosis of glaucoma 
7. Active diabetic retinopathy 
8. Clinically significant inflammation or infection within six (6) months prior to study 
9. Uncontrolled systemic disease (e.g., diabetes, hypertension, etc.) in the opinion of the 
Investigator 
10. Participation in any study involving an investigational drug within the past 30 calendar days, 
or ongoing participation in a study with an investigational material 
11. Intolerance or hypersensitivity to topical anesthetics, antibiotics, steroids or any other 
pharmaceuticals that may be used pre and post surgically 
12. Specifically known intolerance or hypersensitivity to contact lenses or any component of the 
investigative material 
13. A medical condition, serious concurrent illness, or extenuating circumstance that would 
significantly decrease study compliance, including all prescribed follow-up 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 7 of 23 
V1 8/19/11 
14. Any condition that, in the opinion of the investigator, would jeopardize the safety of the 
patient 
15. Pregnancy 
Completion and Termination Criteria 
 
Patient Withdrawal 
Patients are free to withdraw consent and withdraw participation in the study at any time for any 
reason, specified or unspecified, and without penalty or loss of benefits to which the subject is 
otherwise entitled and without prejudice to further treatment.  Subject withdrawal from the study 
must be recorded on the case report form (CRF). A patient may be withdrawn at any time at the 
discretion of the investigator.   
The following may be justifiable reasons for the investigator to withdraw a patient from the 
study: 
 
• 
A patient who is uncooperative or misses two or more consecutive follow-up visits 
• 
A patient noncompliant with the medical study requirements, including the prescribed use 
of medication 
• 
A patient erroneously included in the study 
• 
A patient who develops an exclusion criterion or concurrent disease ( Please note that if 
subject reports pregnancy, that will be considered as developing exclusion criteria at any 
time point as per study protocol and  will be withdrawn from the study.) 
 
Moreover, a patient may be withdrawn from the study for the following medical or administrative 
reasons: 
 
• 
Adverse Event (AE):  If a patient suffers an AE that, in the judgment of the Investigator, 
presents an unacceptable consequence or risk to the patient, the patient will be 
withdrawn from further participation in the study. 
 
If a patient decides to withdraw from participation in the study, every effort should be made to 
contact him or her to obtain information about the reason(s) for withdrawal and about any 
adverse events.  Whenever possible, the patient should return to the study site for final clinical 
assessments.  It is important for the Investigator to provide a written report on the Patient 
Disposition page of the CRF describing the reason for withdrawal. 
 
Study Procedures 
Study Outcomes: 
• 
Degree of pain during the post operative period 
• 
Degree of discomfort during the post operative period 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 8 of 23 
V1 8/19/11 
• 
Ability to function during the post operative period 
• 
Visual acuity recovery during the post operative period 
 
Safety will be evaluated by ocular signs and symptoms, (best corrected) visual acuity and 
occurrence of adverse events. 
 
 
Study Treatment 
The study method is comprised of the placement of an eye shield to the eye after PRK similar to 
standard bandage lens. A standard bandage contact lens may be placed on the eye(s) after 
PRK at the investigator’s discretion. 
 
Methods 
1. Patients planning to undergo PRK will be recruited for the study. 
2. Aside from the procedure described below no alteration in patient management in the 
post PRK period will be made. 
3. Both eyes will be treated in the same manner. 
4. Following detailed explanation and signing an informed consent form each patient will 
receive the following:  
a. Bilateral standard PRK procedure.  A trephine up to 8mm will be used to mark 
the debridement zone.  If the surgeon decides to apply alcohol for debridement, a 
20% alcohol solution placed in the trephine will be used to prepare the cornea for 
debridement. 
b. Standardized mitomycin use to ablation depth > 70 microns 
 
 
(For LASIK re-treatments mitomycin used in all cases) 
c. At the end of the procedure while still on the surgery table1 gtt of Ophthalmic 
Steroid may be administered to both eyes, then the eye shield will be placed on 
the study eye.  A bandage contact lens may be placed at the investigator’s 
discretion. 
At 1hr, 1, 2, 3, 4, 7 days and 1 month following the procedure the patients will undergo the 
following evaluations.  Patients may also be evaluated at days 5 and 6  - at investigator’s 
discretion.  
i. 
Anterior segment examination-all visits 
ii. 
Pain Assessment-all visits, Day 5 and 6 will be optional 
iii. 
Discomfort assessment-all visits, Day 5 and 6 will be optional 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 9 of 23 
V1 8/19/11 
iv. 
Functional assessment-all visits, Day 5 and 6 will be optional 
v. 
Uncorrected visual acuity (UCVA)-all visits 
vi. 
Best corrected visual acuity (BCVA)-all visits, Day 5 and 6 and 1hr will be 
optional 
vii. 
Contrast Sensitivity Test-(optional) 
viii. 
Anterior segment OCT-(optional) 
ix. 
Corneal Topography- required at baseline, post shield removal, follow up visit 
after post shield removal visit, 1 week and 1 month 
x. 
Intraocular Pressure measurement: baseline, 1 week. Measurement at 1 month 
is optional and will be required if IOP at 1 week is increased by 3mmHg or 
higher from the baseline value . 
 
Medications 
Fluorescein will be used for corneal assessments. Topical anesthetics will be used as 
necessary during the procedure.  The following medication regimen will be followed but may be 
adjusted at the investigator’s discretion: 
 
Preop (1 day before surgery): 
• 
Ophthalmic Steroid 1 gtt OU q 2 hrs 
• 
Ophthalmic Antibiotic 1 gtt OU q 2 hrs 
• 
Ophthalmic NSAID 1 gtt OU q 2 hrs 
 
Surgery Day 
• 
Valium 30 minutes before surgery 
Intraop 
• 
Ophthalmic Steroid  
• 
Ophthalmic Antibiotic  
• 
Ophthalmic NSAID  
 
Post Operative Day 0 (Begin after surgery until bedtime) 
• 
Ophthalmic Steroid 1gtt OU q 1 hour 
• 
Ophthalmic NSAID 1gtt OU q 1 hour 
• 
Ophthalmic Antibiotic 1gtt OU q 1 hour 
• 
Ibuprofen 600mg q 4 hour PO  
• 
Ophthalmic Steroid/Lubricant at night 
 
Day 1 & Day 2 (while awake) 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 10 of 23 
V1 8/19/11 
• 
Ophthalmic Steroid 1 gtt OU q 4 hrs 
• 
Ophthalmic Antibiotic 1 gtt OU 4  hrs 
• 
Ophthalmic NSAID 1 gtt OU q 4 hrs 
• 
Ibuprofen 600 mg q 4 hrs 
• 
Ophthalmic Steroid/Lubricant at night 
 
Post Operative Day 3 
• 
Ophthalmic Steroid 1 gtt OU q 4 hrs 
• 
Ophthalmic Antibiotic 1 gtt OU 4  hrs 
• 
Ibuprofen 400 mg q 4 hrs 
 
Post Operative Day4-7 
• 
Ophthalmic Steroid 1 gtt OU q 4 hrs 
• 
Ophthalmic Antibiotic 1 gtt OU 4  hrs 
• 
Ibuprofen PRN 
 
Post Operative Day 8 
• 
Ophthalmic Steroid 1 gtt OU BID x 1 week, QD x 1 week, then stop 
 
 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 11 of 23 
V1 8/19/11 
Time and Events Schedule: The procedures associated with each study visit are outlined and 
summarized in Table 1.  
Table 1: Schedule of Visits and Procedures 
 
Procedure 
 
Baseline 
 
Placement 
(0 hr) 
 
1 
hour 
 
1 day 
 
2 days 
 
3 days   
 
4 days  
 
5 days 
 
 
6 days 
 
1 week 
 
 
1 Month 
+/- 3 day 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8* 
9* 
10 
11 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Ocular History 
X 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Systemic and topical 
medication profile 
X 
 
 
 
 
 
 
 
 
X 
 
Anterior Segment 
Examination including 
the Slit Lamp Exam 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Visual Acuity 
(Uncorrected) (UCVA) 
X 
 
X 
X 
X 
X  
X  
X  
X  
X 
X 
Visual Acuity (Best 
corrected) (BCVA) 
X 
 
 
X 
X 
X 
X 
X  
X  
X 
X 
Contrast Sensitivity 
(optional) 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Subjective pain, 
discomfort and 
function assessment 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Corneal Photography  
X 
(optional) 
 
X 
(optional) 
X 
X 
X 
X 
X 
X 
X 
X 
(optional) 
Corneal Topography 
X 
 
 
X 
(optional) 
X 
(optional) 
X 
(optional) 
X 
(optional) 
X 
(optional) 
X 
(optional) 
X 
X 
OCT (optional) 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
IOP Measurement 
 
X 
 
 
 
 
 
 
 
 
X 
X 
***optional 
unless 1 
week IOP 
value 
changed 
from B/L 
Placement of eye 
shield (and/or 
bandage contact lens) 
 
X 
 
 
 
 
 
 
 
 
 
Removal of  shield 
 
 
 
 
 
X** 
 
 
 
 
 
*If the shield is no longer on the eye, visit 8 and 9 are not required. These visits will be conducted at investigator’s discretion. 
**Removal of shield (and/or bandage contact lens) will be performed at investigator’s discretion.  

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 12 of 23 
V1 8/19/11 
Study Visits and Procedures 
When possible, all examinations will be scheduled for the same time of day and will be performed 
by the same personnel.  Please refer to Appendix 1 for details of examination methods. 
 
Screening 
• 
Participants will be recruited from the Investigators’ patient population and through referrals. 
• 
Once patients are deemed eligible for study participation, patients will be approached for 
potential study participation and signing of the Informed Consent Form (ICF). 
• 
All patients consented for study participation will be entered on a screening/enrollment log. 
 
Visit 1 - Baseline 
• 
The investigator or authorized study staff member will obtain signed informed consent prior to 
enrolling the patient into the study. 
• 
An enrollment log will be maintained to assure that enrollment is conducted in an unbiased 
consecutive manner.   
• 
Demographics, medical and ocular history, as well as concomitant systemic medications will be 
recorded in the case report form (CRF). 
• 
Biomicroscopy (slit lamp exam) with corneal photography (as needed) will be performed. 
• 
Tear film stability will be evaluated using tear breakup time (TBUT). 
• 
Determine subjective pain, comfort and functional assessment 
• 
Uncorrected and best corrected visual acuity will be measured using ETDRS acuity chart. 
• 
Corneal topography 
• 
Intraocular pressure measurement 
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT)- (optional) 
 
Visit 2 - Placement (0 hour) 
The placement of the corneal shield (and/or bandage contact lens) will be performed immediately 
following the PRK procedure (while the patients are still under the laser’s microscope).    
• 
Standard intra-operative PRK medication will be placed on the eye. 
• 
Shield (and/or bandage contact lens) will be placed bilaterally. 
• 
Standard post PRK medical treatment will be initiated 
• 
Any adverse events will be recorded. 
 
Visit 3 - 1 hour Post-PRK 
This examination must occur one hour after placement of the shield (and/or bandage contact lens). 
The following will occur at this examination: 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 13 of 23 
V1 8/19/11 
• 
Record any adverse events. 
• 
Subjective pain and comfort questionnaire 
• 
Perform slit lamp exam, corneal photography (optional) 
• 
UCVA  
 
Visit 4 – 1 day Post-PRK 
This examination must occur the day after placement of the shield (and/or bandage contact lens).  
See patient in the morning. 
The following will occur at this visit: 
• 
Record any adverse events. 
• 
Perform slit lamp exam with corneal photography 
• 
Assessment of tear break up time (TBUT) over the shield 
• 
Transparency assessment of the shield 
• 
BCVA and UCVA  
• 
Determine subjective pain, comfort and functional assessment 
• 
Corneal topography (optional) 
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT) (optional) 
 
Visit 5 – 2 day Post-PRK 
This examination must occur two days after placement of the shield (and/or bandage contact lens).  
See patient in the morning. 
The following will occur at this visit: 
• 
Record any adverse events. 
• 
Perform slit lamp exam with corneal photography. 
• 
Assessment of tear break up time (TBUT) over shield 
• 
Transparency assessment of the shield 
• 
BCVA and UCVA 
• 
Contrast Sensitivity Test (optional) 
• 
Determine subjective pain, comfort and functional assessment 
• 
Corneal topography (optional) 
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT) (optional) 
 
Visit 6 – 3 days Post-PRK 
This visit must occur three days after placement of the shield (and/or bandage contact lens).   
The following will occur at this visit: 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 14 of 23 
V1 8/19/11 
• 
Record any adverse events. 
• 
Perform slit lamp exam with corneal photography 
• 
Assessment of tear break up time (TBUT) over the shield 
• 
Transparency assessment of the shield 
• 
BCVA and UCVA 
• 
Determine subjective pain, comfort and functional assessment 
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT) (optional) 
• 
Removal of the shield and or bandage lens if epithelial defect has close 
• 
Corneal topography (optional) 
 
Visit 7 – 4 days Post-PRK 
This visit must occur four days after placement of the shield (and/or bandage contact lens).   
The following will occur at this visit: 
• 
Record any adverse events. 
• 
Perform slit lamp exam with corneal photography 
• 
Assessment of tear break up time (TBUT) over the shield or without the shield if shield was 
removed  
• 
Transparency assessment of the shield (Required only if shield is present)  
• 
BCVA and UCVA 
• 
Determine subjective pain, comfort and functional assessment 
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT) (optional) 
• 
Removal of the shield and /or bandage lens if not removed at day 3 and epithelium is closed 
• 
Corneal topography: Required for both cases: if shield is not present or if shield is removed at 
day 4 (post shield removal).  
 
Visit 8 & 9-5 & 6 days Post-PRK-If shield is removed, this visit will be at the Investigator’s 
discretion 
The following will occur at this visit: 
• 
Record any adverse events. 
• 
Perform slit lamp exam with corneal photography 
• 
Assessment of tear break up time (TBUT) over the shield or without the shield if shield was 
removed  
• 
Transparency assessment of the shield (Required only if shield is present)  
• 
BCVA and UCVA 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 15 of 23 
V1 8/19/11 
• 
Determine subjective pain, comfort and functional assessment 
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT) (optional) 
• 
Removal of the shield and /or bandage lens if not removed at day 3 and epithelium is closed 
• 
Corneal topography: Required for both cases: if shield is not present or if shield is removed at 
day 4 (post shield removal).  
 
Visit 10 – 1 week Post-PRK 
This visit must occur seven days after placement of the shield (and/or bandage contact lens).   
The following will occur at this visit: 
• 
Record any adverse events 
• 
Perform slit lamp exam with corneal photography 
• 
Assessment of tear break up time (TBUT) 
• 
BCVA and UCVA. 
• 
Determine subjective pain, comfort and functional assessment 
• 
Corneal topography  
• 
Intraocular pressure measurement : Required;  
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT) (optional) 
 
Visit 11 1 month Post-PRK 
This visit must occur thirty days (+/- 3 day) after placement of the shield (and/or bandage contact 
lens).   
The following will occur at this visit: 
• 
Record any adverse events 
• 
Perform slit lamp exam, corneal photography (optional) 
• 
Assessment of tear break up time (TBUT) 
• 
BCVA and UCVA 
• 
Determine subjective pain, comfort and functional assessment 
• 
Corneal topography  
• 
Intraocular pressure measurement: Required-If  IOP at 1wk increased by 3mmHg or higher 
from baseline 
• 
Contrast Sensitivity Test (optional) 
• 
Anterior segment optical coherence tomography (OCT) (optional) 
 
Additional testing may be performed during the course of the study as determined by the investigator. 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 16 of 23 
V1 8/19/11 
 
Unscheduled Visits 
An unscheduled visit will be any visit to the clinical site other than those specified in the protocol. 
The Investigator or trained and qualified investigational staff will perform all procedures necessary 
to evaluate the study participant at these visits and will record the visit in the patient’s chart and on 
the unscheduled visit form in the CRF. 
• 
Any adverse event should be recorded on the adverse event (AE) form in the CRF. 
 
Study Completion 
The trial is completed when the planned enrollment has been completed and the enrolled patients 
exit the study. 
 
Adverse Events and Reportable Adverse Events 
An adverse event is any undesirable clinical event experienced by a patient during participation in 
a clinical trial whether or not that event is considered related to the investigational material.  This 
includes a change in the patient’s condition or laboratory results which has or could have a 
deleterious effect on the patient’s health or well-being.  For example, hospitalization of the patient 
for any reason is considered an adverse event. 
 
Any adverse event reported by a patient or noted by the Investigator must be reported on the 
Adverse Event Case Report Form.  The Investigator must categorize each adverse event by 
degree of harm to the patient (serious or not serious), relationship to study material (definite, 
probable, possible, or no relationship), and whether or not the adverse event was unanticipated 
(listed below are expected/anticipated events for this material).   
 
A finding represents any objective observations made by the Investigator during the examinations.  
An objective finding by the Investigator will be considered an adverse event if: 
• 
It was not present at the previous visit and not considered part of the surgical procedure (i.e.-
epithelial defect) 
• 
It was present at the previous visit(s) but with a lesser severity than the current observation 
 
A symptom is a noticeable change that is perceived by the patient.  Any ocular or systemic 
symptom, which is out of the ordinary for the patient, will be reported as an adverse event.  The 
patient will be directly questioned about symptoms that occur between visits.   
 
Adverse events will be carefully monitored during the study period.  Minimum requirements of data 
to be recorded are: type of event, duration of event (start to end), severity, seriousness, action 
taken, outcome, relationship to material (definitely, probably, possibly, or not related), and, if 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 17 of 23 
V1 8/19/11 
possible, the cause of the event. The investigator shall follow the participant until the condition 
clears, returns to baseline, or no longer warrants further follow-up. 
 
• 
Intra-Operative Adverse Events: 
o Material malfunction identified prior to  placement 
 
• 
Post-Operative Adverse Events: 
o Visual acuity loss determined to be unacceptable as judged by treating physician 
o Pain determined to be unacceptable as judged by treating physician 
o Shield lens malposition 
o Shield malfunction (and/or bandage contact lens) 
o Persistent inflammation after 1 month postop 
o Infection 
o Corneal complications (corneal edema after 1 month, opacification) 
o Corneal sterile infiltrates 
 
Note: Investigator or responsible staff personnel are required to notify the adverse 
events to the Sponsor or designee within 24 hours of knowledge of the event.  The 
Serious Adverse Event/Unanticipated Adverse material Effect form should be completed 
in as much detail as possible and faxed to Sponsor at: 
FAX (for reporting): (650) 618-2522 
 
Phone (for queries): (650) 325-2050 
 
Serious Adverse Events 
Any of the following will be considered a Serious Adverse Event (SAE): 
• 
Death 
• 
Life-threatening event 
• 
In-patient hospitalization or prolongation of existing hospitalization 
• 
Complete loss of vision 
• 
Sight-threatening complication: 
o Endophthalmitis 
 
Trained and competent personnel in recognizing and treating adverse reactions of all types must 
be immediately available; personnel must also have current treatment knowledge. 
 
An event does not need to be reported as a serious adverse event (SAE) if it represents only a 
relapse or an expected change or progression of pain of discomfort typically associated with PRK.  
This type of event needs only to be reported as an adverse event.   

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 18 of 23 
V1 8/19/11 
 
It is the Investigator’s responsibility to inform the appropriate Institutional Review Board (IRB) and 
Sponsor about serious adverse events associated with the Corneal Shield. 
 
Unanticipated Adverse Material Effects 
An unanticipated adverse material effect (UADE) or event is any serious adverse effect on health 
or safety or any life-threatening problem or death caused by, or associated with, a material if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence in 
the investigation plan, or any other unanticipated serious problem associated with a material that 
relates to the rights, safety, or welfare of patients.  The following events are expected after the 
procedure: 
Epithelial defect for up to 7 days 
Redness  
Excessive tearing 
Light sensitivity for up to 3 months 
Corneal edema for up to 1 month 
Pain and discomfort until corneal re-epithelialization 
Increased dryness for up to 6 months 
 
The investigator will be responsible for informing the IRB of the adverse events, serious adverse 
events, or unanticipated adverse material effects that have occurred during the study and that have 
been determined attributable to the study material.    
Statistical Methods  
Since this is an exploratory study and no formal hypothesis testing is planned, a sample size 
estimate has not been calculated. Descriptive statistics will be used to present study outcomes, 
including demographic information, etc. 
Ethical and Regulatory Considerations 
This protocol was designed and will be conducted, recorded, and reported in compliance with the 
principles of Good Clinical Practice (GCP) regulations.  These requirements are stated in global 
regulations as well as “Guidance for Good Clinical Practice”, International Conference on 
Harmonization (ICH), and the most recent guidelines of the Declaration of Helsinki of Technical 
Requirements for Registration of Pharmaceuticals for Human Use. 
 
Institutional Review 
This protocol and patient informed consent form (ICF) must be reviewed and approved by an 
Institutional Review Board (IRB) before enrollment of patients.   
 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 19 of 23 
V1 8/19/11 
It is the responsibility of the Investigator to obtain approval for the Study Protocol and to keep the 
Institutional Review Board informed of serious adverse events and any amendments to the 
protocol.  It is also the Investigator’s responsibility to maintain a file of all correspondence with the 
Institutional Review Board  
 
Changes to the Study Protocol or Conduct of the Study 
All changes must be documented by signed protocol amendment.  If substantial changes to the 
design of the study are made, the amendment must be submitted to and approved by the IRB and 
must be agreed to and signed by the Investigator.    
 
Patient Informed Consent 
Written informed consent is required prior to enrollment in the study.  It is the responsibility of the 
Investigator to obtain such consent.  
 
Case Report Forms 
Case Report Forms (CRFs) are provided separately from this clinical protocol document. CRFs will 
be filled out legibly and completely (black or blue ball point pen).  The original and copy of CRFs 
will be kept by the investigator.   
 
Each patient enrolled in the study will be assigned a unique patient number.  The patient identifier 
will include the enrollment number. As the person ultimately responsible for the accuracy of all CRF 
data, the Investigator must sign each patient’s CRF.   
 
All study-required data will be completely documented in patient study files. 
 
Study Material Information and Accountability 
 
Coding/Masking:  As this is a non-comparative study, no coding or masking will be used. 
 
Dispensing:  The Investigator, or designee, will be responsible for keeping current and accurate 
records of the materials dispensed.  
 
Declaration of Helsinki 
The study will be performed in accordance with the recommendations guiding physicians in 
biomedical research involving human subjects adopted by the 18th World Medical Assembly, 
Helsinki, Finland, 1964 and later amendments. 
 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 20 of 23 
V1 8/19/11 
The investigator must retain patient identification codes after the completion or discontinuation of the 
trial.  Patient files and other source data must be kept for the maximum period of time permitted by 
the practice.   
 
Regulatory Requirements 
 
Anonymity 
The anonymity of participating patients must be maintained.  Patients are identified by their initials 
and assigned a patient identification number on CRFs and other documents.  Documents not 
submitted that identify the patient (e.g., the signed informed consent document) must be 
maintained in strict confidence by the investigator. 
 
Monitoring  
The Sponsor or Sponsor representative may visit the investigator periodically for the purpose of 
monitoring the progress of this study in accordance with GCP regulations.  It is the responsibility of 
the investigator to be present or available for consultation during such scheduled monitoring visits.  
During these routine visits, all data pertaining to a patient's participation in this clinical investigation 
must be made available to the monitor.  Monitoring will include personal visits and other forms of 
communication to assure that the investigation is conducted according to protocol and in order to 
comply with guidelines of good clinical practice.  On-site review of CRFs will include a review of 
forms for completeness and clarity, and for consistency with source documents.  Note that a variety 
of original documents, data, and records will be considered as source documents in this trial.   A 
copy of the patient’s study laboratory values will be added to the CRF, and the original document 
will remain in the source document file. 
 
The Sponsor or Sponsor representative may request to witness patient evaluations occurring as 
part of this protocol.  The Investigator and appropriate personnel may be periodically requested to 
attend meetings/workshops organized by the Sponsor to assure acceptable protocol execution.   

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 21 of 23 
V1 8/19/11 
APPENDIX 1 
 
Examination Procedures, Tests, Equipment and Techniques 
 
 
Visual Acuity (uncorrected) 
 
Introduction: Distance uncorrected visual acuity will be measured at baseline and follow-up visits 
as shown in Table 1. Standard ETDRS acuity chart will be used for measuring VA. 
 
In order to provide standardized and well-controlled assessment of visual acuity during the study, 
all visual acuity assessments for a subject must be performed consistently (e.g., the same lighting 
conditions, viewing distance, etc.) during the entire study. 
 
Scoring Best-Corrected Visual Acuity 
 
While looking through the manifest refraction in the phoropter giving the best vision according to 
the patient and the patient properly aligned with the ETDRS chart, the patient should be asked to 
read the smallest line that he can distinguish on the chart. If the patient chooses a line and reads it 
perfectly, he should be encouraged to read the next smallest line and so on until he makes errors 
in reading a line. The visual acuity is the largest Snellen fraction corresponding to the line of 
smallest letters that the patient can read with two or less mistakes. If one line is read with two 
mistakes and the next smallest line is read with three letters misread, the visual acuity should be 
recorded as the Snellen fraction corresponding to the line that was read with two mistakes, using “-
2” to indicate the 2 mistakes. This will indicate the number of correct letters read by the subject.  
 
Biomicroscopy 
 
External examination and biomicroscopy will be performed using a slit lamp.  Magnification will be 
consistent with standard clinical practice. 
 
Observations will be documented on the appropriate Case Report Form: 
 
The clinician will examine the conjunctiva, cornea, anterior chamber of the eye with the aid of a slit 
lamp, which is a table-mounted binocular microscope.  Fluorescein dye will be instilled into the 
ocular cul-de-sac to facilitate this examination as indicated by the study method section.  The 
patient will be seated during the examination.  Grading will be done as follows: 
 
 
CORNEA  
Edema 
None (0)= 
Transparent and clear or less than mild 
Mild (+1) = 
Dull glassy appearance 
Moderate (+2)= 
Dull glassy appearance of epithelium with large number of vacuoles 
Severe (+3) = 
Epithelial bullae and/or stromal edema, localized or diffuse, with or without stromal 
striae 
 
 
 
Staining/Erosion 
None (0)= 
No fluorescein staining of epithelium, OR less than mild 
Mild (+1) = 
Slight fluorescein staining confined to a small focus 

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 22 of 23 
V1 8/19/11 
Moderate (+2)= 
Regionally dense fluorescein staining (1 mm or greater in diameter) with underlying 
structure moderately visible 
Severe (+3) = 
Marked fluorescein staining or epithelial loss 
 
ANTERIOR CHAMBER (Anterior Segment) 
Cells 
None (0)= 
No cells seen or less than mild 
Mild (+ 1) = 
+ cells 
Moderate (+2) = 
++ cells 
Severe (+3) = 
+++ cells 
Hypopyon (+4)= 
++++ cells, Hypopyon Formation (indicate size of hypopyon) 
 
Flare 
None (0)= 
No Tyndall effect or less than mild 
Mild (+1) = 
Tyndall beam in the anterior chamber has a mild intensity 
Moderate (+2) = 
Tyndall beam in the anterior chamber is of strong intensity 
Severe (+3) = 
Tyndall beam is very intense.  The aqueous has a white, milky appearance 
 
Photography 
 
As part of the biomicroscopic examination, photographs may be taken by the investigator or staff to 
document the status of the shield/bandage contact lens, ocular conditions, or other observations 
made by the Investigator.  These are to be taken consistent with standard clinical practice.  The 
patient’s name or identifying features should not be included. 
 
References 
1.    Schallhorn SC, Farjo AA, Huang D, Boxer Wachler BS, Trattler WB, Tanzer DJ, Majmudar    
       PA, Sugar A; American Academy of Ophthalmology. Wavefront-guided LASIK for the   
       correction of primary myopia and astigmatism a report by the American Academy of   
       Ophthalmology. Ophthalmology. 2008 Jul;115(7):1249-61. 
2.    Alió JL, Muftuoglu O, Ortiz D, Pérez-Santonja JJ, Artola A, Ayala MJ, Garcia MJ, de Luna     
       GC. Ten-year follow-up of laser in situ keratomileusis for high myopia. Am J Ophthalmol.    
       2008 Jan;145(1):55-64. 
3.    Ghadhfan F, Al-Rajhi A, Wagoner MD. Laser in situ keratomileusis versus surface ablation:   
       visual outcomes and complications. J Cataract Refract Surg. 2007 Dec;33(12):2041-8.  
4.    Kymionis GD, Tsiklis N, Karp CL, Kalyvianaki M, Pallikaris AI. Unilateral corneal ectasia   
       after laser in situ keratomileusis in a patient with uncomplicated photorefractive keratectomy   
       in the fellow eye. J Cataract Refract Surg. 2007 May;33(5):859-61.  
5.    Javadi MA, Mohammadpour M, Rabei HM. Keratectasia after LASIK but not after PRK in  
       one patient. J Refract Surg. 2006 Oct;22(8):817-20. 
6.    Rao SK, Srinivasan B, Sitalakshmi G, Padmanabhan P. Photorefractive keratectomy versus  
       laser in situ keratomileusis to prevent keratectasia after corneal ablation. J Cataract Refract  
       Surg. 2004 Dec;30(12):2623-8.30.   
7.    El-Maghraby A, Salah T, Waring GO 3rd, Klyce S, Ibrahim O. Randomized bilateral   
       comparison of excimer laser in situ keratomileusis and photorefractive keratectomy for 2.50  
       to 8.00 diopters of myopia. Ophthalmology. 1999 Mar;106(3):447-57 
8.    Solomon KD, Donnenfeld ED, Raizman M, Sandoval HP, Stern K, VanDenburgh A,  
       Cheetham JK, Schiffman R; Ketorolac Reformulation Study Groups 1 and 2. Safety and  
       efficacy of ketorolac tromethamine 0.4% ophthalmic solution in post-photorefractive   
       keratectomy patients. J Cataract Refract Surg. 2004 Aug;30(8):1653-60.  
9.    Nissman SA, Tractenberg RE, Babbar-Goel A, Pasternak JF. Oral gabapentin for the   
       treatment of postoperative pain after photorefractive keratectomy. Am J Ophthalmol. 2008  
       Apr;145(4):623-629. Epub 2008 Jan 28.  

Corneal Shield for Mitigating Pain Post-PRK 
Protocol 
 
 
 
CONFIDENTIAL 
Page 23 of 23 
V1 8/19/11 
10.  Lim-Bon-Siong R, Valluri S, Gordon ME, Pepose JS. Efficacy and safety of the ProTek   
       (Vifilcon A) therapeutic soft contact lens after photorefractive keratectomy.Am J   
       Ophthalmol. 1998 Feb;125(2):169-76. 
11.  Gruenauer-Kloevekorn C, Kloevekorn-Fischer U, Duncker GI. Contact lenses and special   
       back surface design after penetrating keratoplasty to improve contact lens fit and visual  
       outcome. Br J Ophthalmol. 2005 Dec;89(12):1601-8. 
12.  El-Agha MS, Johnston EW, Bowman RW, Cavanagh HD, McCulley JP. Photorefractive   
       keratectomy versus laser in situ keratomileusis for the treatment of spherical hyperopia.   
       Eye Contact Lens. 2003 Jan;29(1):31-7. 
13.  Gallar J, Acosta MC, Gutiérrez AR, Belmonte C.  Impulse activity in corneal sensory nerve    
       fibers after photorefractive keratectomy. Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4033-7. 
14   Gurland JE. Use of Silicone Lenses in Infants and Children, Ophthalmology 1979; 86:1599-   
       1604. 
15.  Aasuri MK, Venkata N, Preetam P, Rao NT.  Management of pediatric aphakia with silsoft  
       contact lenses. CLAO J. 1999 Oct; 25(4):209-12.