Protease and Cytokine Composition in Post Lens Tear Reservoir of Scleral Lenses for Keratoconic Eyes
Phase: NA
Conditions: Keratoconus
Sponsor: University of Waterloo

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Page 1 
School of 
University of Waterloo 
519-888-4567, ext. 33085 
Optometry and Vision 
200 University Avenue West 
Fax 519-746-5977 
Science 
Waterloo, Ontario, Canada  
optometry@uwaterloo.ca 
Faculty of Science 
N2L 3G1 
 
www.optometry.uwaterloo.ca 
 
 
 
 
 
Protocol 
 
Protease and cytokine composition in post lens tear reservoir of scleral 
lenses for Keratoconic eyes 
 
Protocol author:  Debby Yeung OD, BSc  
 
Principal Investigator(s):  
Debby Yeung OD, BSc    
 __________________________________________________                
Co-Investigator: 
Luigina Sorbara OD, MSc 
___________________________________________________ 
 
 

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Table of Contents 
1 
Introduction .......................................................................................................................... 5 
2 
Purpose and hypothesis ...................................................................................................... 5 
3 
Objectives ............................................................................................................................ 5 
4 
Materials and methods ......................................................................................................... 6 
4.1 
Study design ................................................................................................................. 6 
4.1.1 
Overall design ........................................................................................................ 6 
4.2 
Study Population ........................................................................................................... 6 
4.2.1 
Sample size calculation .......................................................................................... 6 
4.2.2 
Number of participants ........................................................................................... 6 
Inclusion criteria ................................................................................................................... 6 
Exclusion Criteria ................................................................................................................. 7 
4.3 
Study materials ............................................................................................................. 7 
4.3.1 
Visante OCT ........................................................................................................... 7 
4.3.2 
Pentacam ............................................................................................................... 7 
4.3.3 
Keratograph 4 ......................................................... Error! Bookmark not defined. 
4.3.4 
Semi-scleral lenses ................................................................................................ 8 
4.3.5 
Tear Film Analysis .................................................................................................. 8 
4.4 
Scheduled and unscheduled visits ................................................................................ 8 
4.4.1 
Screening ............................................................................................................... 8 
4.4.2 
Study visits ............................................................................................................. 8 
4.4.3 
Unscheduled visits ................................................................................................. 9 
4.5 
Study procedures .......................................................................................................... 9 
4.5.1 
Screening, Baseline and experimental measurements ........................................... 9 
5 
Potential Risks and Benefits to Human Subjects ................................................................ 12 
6 
Unintended events ............................................................................................................. 12 
7 
Discontinuation from the study ........................................................................................... 13 

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8 
Study completion and remuneration................................................................................... 13 
9 
Statistical analysis and data management ......................................................................... 14 
9.1 
Statistical analysis ....................................................................................................... 14 
9.2 
Data management ....................................................................................................... 14 
10 
Protocol training ................................................................................................................. 14 
11 
Study monitoring ................................................................................................................ 14 
12 
Study management ............................................................................................................ 15 
12.1 
Statement of compliance ......................................................................................... 15 
12.2 
Ethics review............................................................................................................ 15 
12.3 
Adverse Events ........................................................................................................ 15 
12.3.1 
Adverse Event Definitions .................................................................................... 15 
12.3.2 
Procedures for Adverse Events ............................................................................ 17 
12.4 
Protocol deviations .................................................................................................. 18 
12.4.1 
Major protocol deviations ...................................................................................... 18 
12.4.2 
Minor protocol deviations ...................................................................................... 18 
12.4.3 
Reporting and documenting protcol deviations ..................................................... 19 
12.5 
Premature termination of the study .......................................................................... 19 
13 
Quality Assurance .............................................................................................................. 19 
13.1 
Study participant records ......................................................................................... 19 
13.2 
Retention of study records and data ........................................................................ 19 
14 
Clinical Trial Registration ................................................................................................... 20 
15 
Report ................................................................................................................................ 20 
16 
Appendices ........................................................................................................................ 20 
17 
References ........................................................................................................................ 20 
 
 
 

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 Confidentiality 
This is a private document and the property of the School of Optometry and Vision Science. It 
is therefore confidential to the recipient and must not be quoted from or distributed beyond the 
company to which it is sent without the express written permission of the Principal Investigators 
(or her/his designate). Release of information from this document is governed by the research 
agreement on file. 
 
Disclaimer 
This study will be conducted for research purposes only and is not intended to be used to support safety 
and efficacy in a regulatory submission. 
 
 
 
 

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14 INTRODUCTION 
Scleral contact lenses are rigid gas permeable lenses designed to rest on the sclera while 
vaulting over the cornea with a fluid reservoir. (1) The use of scleral contact lenses has become 
the current standard of practice as a nonsurgical management of corneal ectasia and ocular 
surface diseases.(1–3) Currently, the long term impact which scleral contact lens wear has on 
the physiology of the cornea and limbus is not known. Tear film analysis of changes in levels of 
proteinases and cytokines have helped researchers gain a better understanding of 
pathophysiology in complications in soft contact lenses wearers (4,5), dry eye (6), and 
keratoconus (7,8). Understanding factors that influence tear film composition may aid in better 
understanding of the impact of scleral contact lenses on the health of the cornea, specifically, the 
mechanism of complications commonly associated with the usage of these large gas permeable 
lenses.  
14 PURPOSE AND HYPOTHESIS 
The purpose of this study is to investigate changes in the level of inflammatory mediators in the 
tear film of scleral contact lenses wearers. The hypothesis is that scleral contact lens wear is 
associated with inflammation in the tear film. Furthermore, the level of proteases and cytokines 
will be altered in samples collected post scleral lens wear compared to those collected pre-lens 
wear. Additionally, the amount of alteration will correlate to the fitting characteristics in the limbal 
zone of the scleral lenses.  
14 OBJECTIVES 
We propose to take a sample of keratoconic participants and fit them in scleral lenses and: 
1. To collect and examine tear samples before and after 6-8 hours of scleral lens wear. 
2. To measure the level proteases and cytokines in each of the samples using enzyme-
linked immunosorbent assays (ELISA) 
3. To compare the results of varying limbal clearance in scleral lens fit. 
 
 

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14 MATERIALS AND METHODS 
13.1 STUDY DESIGN 
12.1.1 OVERALL DESIGN  
This will be a prospective cross-over, dispensing study design.  The study will involve up to 20 
keratoconic participants.  
Participants will attend 1 screening/fitting visit wearing their habitual contact lenses where the 
two test lens designs will be fitted.  There then will be a dispensing visit for each design 
(randomly selected) and a single follow up visit 2 weeks later after 6-8 hours of scleral lens wear. 
A washout period of a minimum of 72 hours will be applied between the cross-over of each lens 
design.  
Lenses to be worn in this study will be made of Boston XO material and are approved by Health 
Canada.  The lenses will have a diameter of 14.8 to 17.8mm with a high and low sagittal depth at 
the limbal zone. As to which of the two lenses is being assessed, both the investigator and the 
participant will be masked. 
13.2 STUDY POPULATION 
12.2.1 SAMPLE SIZE CALCULATION 
A sample of 15-20 participants was chosen according to historical data on tear assessment in 
this group of participants. 
12.2.2 NUMBER OF PARTICIPANTS 
Recruitment:  Up to 20 participants will be enrolled. Participants who are patients of the 
University of Waterloo Contact Lens Clinic (UW-CLC) will be invited to participate in this study by 
their attending doctor. With the patient’s permission, the investigators will initiate recruitment 
according to the in-person script approved by the Office of Research Ethics (Appendix 1). The 
investigators will discuss the project where any questions regarding the study procedures and 
any risks associated with the study can be answered. Eligibility will be determined using the 
inclusion and exclusion criteria. Informed consent will be obtained for all participants prior to their 
enrollment in the study (Appendix 2).   
INCLUSION CRITERIA 
A person is eligible for inclusion in the study if he/she:  
 
Had been diagnosed with keratoconus in at least one eye.  

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 
Is at least 18 years of age and has full legal capacity to volunteer.  
 
Has read and understood the information consent letter.   
 
Is willing and able to follow instructions and maintain the appointment schedule.  
EXCLUSION CRITERIA 
A person will be excluded from the study if he/she: 
 
Is using any topical medications that will affect ocular health.  
 
Has any ocular pathology or severe insufficiency of lacrimal secretion (severe dry eyes) 
that would affect the wearing of contact lenses.  
 
Has persistent, clinically significant corneal or conjunctival staining using sodium 
fluorescein dye.  
 
Has any clinically significant lid or conjunctival abnormalities and active 
neovascularization.  
 
Is aphakic.  
 
Has undergone any corneal surgery.  
 
Is participating in any other type of eye related clinical or research study. 
 
Has any known allergies or sensitivity to the diagnostic pharmaceuticals or products, 
such as fluorescein, used in this study.  
 
13.3 STUDY MATERIALS 
12.3.1 VISANTE OCT 
The Visante OCT Optical Coherence Tomographer, a standard optometric class II medical 
device, commercially available in Canada (Health Canada licence #69113), will be used to 
measure the shape of the eye for contact lens fitting. 
12.3.2 PENTACAM  
The Oculus Pentacam®, a standard optometric class II medical device, commercially available 
in Canada (Health Canada licence #69466) will be used for the measure the corneal curvature.  
12.3.3 KERATOGRAPH 4  
The Oculus Keratograph® 4, a standard optometric class II medical device, commercially 
available in Canada (Health Canada licence #90001) will be used for the limbal and bulbar 
redness evaluation and pre-lens non-invasive tear break-up time (NITBUT) measurements. 
 

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12.3.4 SEMI-SCLERAL LENSES 
The lenses used in this study are approved by Health Canada, with Health Canada license # 
29758, and are commercially available.   All lenses will be worn during the day only. Lenses will 
be fitted according to manufacturer’s recommended guidelines and participants will proceed in 
the study only if a suitable fit with the lenses can be obtained. Appendices 9 (Package insert for 
Boston XO) and 10 (Custom Stable Fitting Guide) are included. 
12.3.5 TEAR FILM ANALYSIS 
Tear film analysis is performed using antigen capture enzyme linked immunosorbent assay 
(ELISA). (5) After collection, the tear samples are stored at -80ºC until analysis. Preparation of 
the samples includes dilution with phosphate buffered saline (PBS) containing 1% (w/v) bovine 
serum albumin and incubation with specific antigen. The tears are assayed for specific 
proteinase and cytokines using commercially available ELISA kits. Preparation and analysis of 
samples are as per instructions supplied by manufacturers.  
13.4 SCHEDULED AND UNSCHEDULED VISITS 
This study has a total of 6 study visits, including the screening visit (see Table 1).  
12.4.1 SCREENING  
The investigator will determine participant eligibility by reviewing the inclusion and exclusion 
criteria. Ineligible participants will be advised they do not meet the criteria for the study. 
12.4.2 STUDY VISITS 
This study will involve 6 visits over 5 study days. The total time commitment for all study visits is 
approximately 6 hours. The total study visit time commitment may be different for each 
participant, as the needed visit time will depend on how easily the lenses can be fitted. 
The first visit will involve screening of the participants and baseline measurements. The 
investigator will determine the eligibility of the participant using the inclusion/ exclusion criteria. 
Ineligible participants will be discontinued from the study. The investigator will also perform 
baseline tear collection. 
At the lens fitting appointment, the participants will be fitted with the scleral contact lenses based 
on the baseline measurement obtained at the screening appointment. Participants will be 
instructed on insertion, removal, and proper handling of the lenses.  

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At each of the lens delivery appointments, the researcher will deliver the study lenses. 
Measurements, including bulbar hyperemia and pre-lens NITBUT, will be obtained while the 
participants are wearing the lenses. 
After the participant has worn the lenses during the day for two weeks, the participant will return 
for a follow up visit. At each of the follow up appointments, the lens fit and measurements, 
including bulbar hyperemia and pre-lens NITBUT, will be repeated while the participants are 
wearing the lenses. Tear samples will be collected from the study lenses after lens removal.  
A wash-out period of minimum of 72 hours is required between the first follow up visit and the 
second lens delivery visit.  
Table 1 provides a summary of the study visits.  
Table 1: Summary of visits 
Visit code 
Visits 
Time 
0-0  
Screening and baseline 
measurements 
1hr±½ hr 
1-1 
Lens fitting 
1hr±½ hr 
2-1 
Lens Delivery visit - Lens 1  
1hr±½ hr 
2-2 
Follow-up visit - Lens 1  
1hr±½ hr 
3-1 
Lens Delivery visit - Lens 2  
1hr±½ hr 
3-2 
Follow-up visit - Lens 2  
1hr±½ hr 
12.4.3 UNSCHEDULED VISITS 
Unscheduled visits will be performed if necessary.   
13.5 STUDY PROCEDURES 
12.5.1 SCREENING, BASELINE AND EXPERIMENTAL MEASUREMENTS 
Screening & Baseline procedure: Participants will present to the screening visit. Their corneal 
sagittal depth which will be measured with the Visante OCT, auto-refraction and associated 
visual acuity measurements and corneal topography carried out and biomicroscopy performed, 
along with hyperemia imaging and pre-lens non-invasive tear break up time. Eligibility will be 
confirmed and a baseline biomicroscopy assessment will be performed. (Visit 0-0)  

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Bulbar and Limbal Redness assessment: The eyes of the participants will be imaged using 
the Keratograph® 4. Participants will be asked to be seated at the Keratograph 4 instrument and 
will be asked to blink 2-3 times and hold their eye open for a few seconds until the instrument 
software takes a picture of the eye. This image will be repeated three times.  
Flush tear collection method: This procedure entails the instillation of a small amount non-
preserved saline, 60µL, into the inferior palpebral fold. After which, the fluid can be collected with 
a micro-capillary tube. (9,10) All samples are collected by the researcher. (Visit 0-0) 
Fitting of the semi-scleral lenses: Participants will be fitted each of the two sets of semi-scleral 
lenses of varying sagittal depth at the limbal zones. Fittings will be done using the corneal 
sagittal depth which was measured at the screening/baseline visit with the Visante OCT. The 
lenses will be made of the same gas permeable lens material Boston XO. The lens fit will be 
evaluated; over-refraction and visual acuity determined. Participants will be instructed on 
insertion, removal, and proper handling of lenses.  (Visits 1-1) 
Video Imaging procedure with test lenses: The lens fitting will be imaged using a video-slit 
lamp and the Visante OCT after the lens delivery appointment (Visits 2-1 & 3-1) and at the follow 
up appointment. (Visits 2-2 & 3-2) 
Pre-lens Non-invasive tear break up time (NITBUT) with test lenses: Pre-lens NIBUT will be 
measured with the study lens after lens delivery (Visits 2-1 & 3-1) as well as at the follow up 
visits (Visits 2-2 & 3-2). Participants will be asked to be seated at the Keratograph 4 instrument 
and will be asked to blink 2-3 times and hold their eye open for a few seconds until the 
instrument software takes a measurement of the NITBUT. This measurement will be repeated 
three times.  
Subjective ocular symptom assessment: At the follow up appointment, participants will be 
asked to rate their ocular comfort, dryness, burning and vision with the contact lenses (Appendix 
5). (Visits 2-2 & 3-2) 
Table 2 lists a summary of procedures to be conducted at scheduled visits. 
 
 

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Table 2: Summary of procedures to be conducted at scheduled visits 
Visit 
Procedure 
Instrument/ 
application 
Form (Appendix #) 
Screening & Baseline 
visit (0-0) 
Informed Consent 
- 
 
ICL (2) 
Demographics & History, 
incl. health, meds, 
contact lens details 
- 
 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
 
Baseline Tear Collection 
- 
 
Biomicroscopy Form (4) 
Sagittal depth 
measurement 
Visante OCT 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
Auto-refraction/ 
topography 
Auto-refractor/ 
Pentacam 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
Vision assessment 
Vision charts 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
Slit-lamp biomicroscopy 
(Corneal integrity & 
staining) 
Slit-lamp 
Biomicroscopy Form (4) 
Hyperemia / NITBUT 
Keratograph 4 
Biomicroscopy Form (4) 
Lens Fitting (Visits 1-1)  
Lens Insertion 
- 
 
- 
 
 
Lens examination 
Slit lamp 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
Lens Delivery (Visits 1-1 
& 2-1) 
Lens examination 
Slit lamp 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
 
Auto-refraction/ 
topography 
Auto-refractor 
/Pentacam 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
 
Vision with study lens 
Vision charts 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
 
Subjective Best Sphere 
Vision charts 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
 
Hyperemia / NITBUT 
Keratograph 4 
Biomicroscopy Form (4) 
 
Ocular Symptom 
Questionnaire 
- 
 
Ocular Symptom Questionnaire (5) 
Follow-up visit (Visits 1-2 
& 2-2) 
Lens examination 
Slit lamp 
Screen/Fitting and Study Visit Form 
for GP Lenses (3) 
 
Hyperemia / NITBUT 
Keratograph 4 
Biomicroscopy Form (4) 
Ocular Symptom 
Questionnaire 
- 
 
Ocular Symptom Questionnaire (5) 
Lens Removal 
- 
 
- 
 
Slit-lamp biomicroscopy 
(Corneal integrity & 
staining) 
Slit-lamp 
Biomicroscopy Form (4) 
 
Tear Sample Collection 
from Lens after Lens 
Removal 
- 
 
Biomicroscopy Form (4) 

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14 POTENTIAL RISKS AND BENEFITS TO HUMAN SUBJECTS 
There may be direct benefits to the participants in this study as they will experience a new lens 
fitting modality. Participation in this study may contribute to scientific research information that 
may be used in the development of new contact lens products.  
This study is considered to be a non-significant risk study based on United States Food and 
Drug administration (FDA) and International Standards Organization (ISO) guidelines due to the 
daily wear nature of the study.   
The lenses used in this study are approved by Health Canada and commercially available. The 
lenses are intended for daily wear (NOT extended wear). This study is a dispensing study. The 
participants’ lens wear will be monitored closely by the investigators as participants will be able 
to be in close contact with the investigator by phone at any time.  
Complications that may occur during the wearing of contact lenses include discomfort, dryness, 
aching or itching eyes, excessive tearing, discharge, hyperemia and variable or blurred vision.  
More serious risks may include photophobia, iritis, corneal edema or eye infection.  Although 
contact lens-related infections are very infrequent with gas permeable rigid lenses, the possibility 
does exist.  The occurrence rate of incurring a bacterial infection for patients that wear rigid gas 
permeable lenses is approximately two/10,000 per year. (11)  
If the participant should experience any pain or discomfort during lens wear, any of the 
symptoms described above, or there is any health concern or a case of emergency, they are 
instructed to contact Dr. Yeung or Dr. Sorbara at (416)-624-7167 or (519) 888-4567 extension 
33085, respectively.  
Although participants with any known allergies or sensitivity to the diagnostic pharmaceuticals or 
products, drops such as fluorescein, used in this study would have been excluded, if any 
irritation occurs the participant will be instructed to contact the investigators. 
14 UNINTENDED EVENTS 
The imaging procedures outlined in this protocol will be carried out with instruments that are 
typically used in any optometric practice and therefore, there are no anticipated unintended 
events. 
 
 

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14 DISCONTINUATION FROM THE STUDY 
Participants discontinued from a study will be compensated $20 for each attended visit in the 
study. Participants will be discontinued at the discretion of the investigators or participant. The 
following is a list of possible reasons for discontinuation from the study: 
 
Screening failure: Participants will be discontinued if they do not meet the inclusion and 
exclusion criteria outlined in section 4.2.2. 
 
Positive slit lamp finding:  Participants may be permanently discontinued from the study 
depending on the severity of the condition and on the judgement of the investigator.   
 
Unexpected adverse event: If a participant experiences an adverse event (excessive 
redness or dryness), at the discretion of the investigator, the participant may be excluded 
from the study.  
 
Symptoms: If the participant has persistent symptoms (excessive redness or dryness), 
the participant may be discontinued from the study based on the clinical judgement of the 
investigator. 
 
Disinterest, relocation or illness: The participant may choose to discontinue due to 
reasons within or beyond their control. 
 
Violation of protocol or non-compliance:  The participant will be discontinued if they are 
unable or unwilling to follow the protocol specified visit schedules and/or study 
procedures. 
 
Lost to follow-up:  The participant will be discontinued if they cannot be contacted and 
does not return for a final exit visit, and if the investigator has made a reasonable effort to 
contact the participant for a final study visit. 
 
Premature termination of the study by the Office of Research Ethics at the University of 
Waterloo. 
 
14 STUDY COMPLETION AND REMUNERATION 
Once their involvement in the study is complete, participants will be informed about receiving 
feedback following study completion in the Letter of Appreciation (Appendix 6). 
Participant remuneration will be up to $120 for completing the study and is typically paid at the 
end of the study (Appendix 7). 

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14 STATISTICAL ANALYSIS AND DATA MANAGEMENT 
13.1 STATISTICAL ANALYSIS 
All data described above will be analysed at the University of Waterloo from the eye(s) wearing 
the semi-scleral contact lens(es).  Data analysis will be conducted using Statistica 12.  
Descriptive statistics will be provided on information regarding baseline variables (age, gender, 
sagittal depth distribution, etc.). Table 3 lists the primary outcome variables and anticipated 
statistical procedures. 
Table 3: Statistical procedures 
Variable 
Analysis 
Statistical test 
Parametric (tear 
clearance, NIBUT, 
comfort ratings, tear 
components)  
Comparison of lens 1 to lens 2 
ANOVA 
Paired t-test 
13.2 DATA MANAGEMENT 
At the completion of the study, a report will be generated. Data from this study will be referred to 
only using study number and will be retained by the PI’s for a minimum of 25 years on a 
password-protected server held by Dr Sorbara. After 25 years, data will be disposed of in 
accordance with the guidelines laid out by the University of Waterloo. 
14 PROTOCOL TRAINING 
Training of the research assistant will be conducted for this study to educate her about the 
testing procedures.  
14 STUDY MONITORING 
Study records may be inspected by the investigator’s supervisor,  the Office of Research Ethics 
at the University of Waterloo, and by regulatory authorities in Canada (Health Canada); however, 
no records containing identifiable/personal information will be permitted to leave the School of 
Optometry and Vision Science, Contact Lens Clinic. 
 
 

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STUDY MANAGEMENT 
13.1 STATEMENT OF COMPLIANCE 
This clinical study is designed to be in compliance with the ethical principles in the Declaration of 
Helsinki, with the ICH guidelines for Good Clinical Practice (GCP), with the University of 
Waterloo’s Guidelines for Research with Human Participants and with the Tri-Council Policy 
Statement: Ethical Conduct for Research Involving Humans, 2nd Edition. 
 
Declaration of Helsinki 
 
ICH E6 - International Conference on Harmonisation; Good Clinical Practice 
 
http://iris.uwaterloo.ca/ethics/human/guidelines/index.htm 
 
http://iris.uwaterloo.ca/ethics/human/ethicsReview/UWStatement.htm 
 
http://www.pre.ethics.gc.ca/eng/policy-politique/initiatives/tcps2-eptc2/Default/ 
 
13.2 ETHICS REVIEW 
This protocol will be submitted to the Office of Research Ethics (ORE) at the University of 
Waterloo and reviewed by the Clinical Research Ethics Committee. Notification of ethics 
clearance of the application is required prior to the commencement of the study. 
13.3 ADVERSE EVENTS 
12.3.1 ADVERSE EVENT DEFINITIONS 
An ‘adverse event’ refers to any undesirable clinical occurrence in a participant, whether it is 
considered to be device-related or not. Adverse events (AE) may be classified as ‘unanticipated 
adverse device effects,’ ‘serious adverse events,’ ‘significant adverse events,’ or ‘non-significant 
adverse events,’ as defined below. 
 

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AE classification, coding and examples are provided in the following table used for reporting.  
Code 
Condition 
Reporting 
Serious Adverse Events 
01 
Presumed infectious keratitis or infectious corneal ulcer 
Notify ORE as 
soon as possible, 
within 24 hours;  
02 
Permanent loss of ≥ 2 lines of best spectacle corrected visual acuity (BSCVA) 
03 
Corneal injury that results in permanent opacification within central cornea 
(6mm) 
04 
Uveitis or Iritis (e.g. presence of anterior segment inflammation as described 
in ISO 11980, Annex B) 
05 
Endophthalmitis 
06 
Hyphema 
07 
Hypopyon 
08 
Neovascularization within the central 6mm of cornea 
00 
Other serious event 
Significant Adverse Events 
11 
Peripheral (outside central 6mm), non-progressive, non-infectious ulcer 
Notify ORE as 
soon as possible, 
within 5 working 
days;  
12 
Symptomatic corneal infiltrative event 
13 
Superior epithelial arcuate lesions (SEALs) involving epithelial split 
14 
Corneal staining ≥ dense coalescent staining up to 2mm in diameter (e.g. 
moderate, ISO 11980 grade 3) 
15 
Corneal neovascularization ≥ 1.0mm vessel penetration  
(e.g. ≥ ISO 111980 Grade 2), if 2 grade change from baseline 
16 
Any temporary loss of ≥ 2 lines BSCVA for ≥ 2wks 
17 
Any sign and/or symptom for which participant is administered therapeutic 
treatment or which necessitates discontinuation of lens wear for ≥ 2 weeks 
10 
Other significant event 
 
 
Classification 
Definition 
Serious Adverse 
Event 
Those events that are life-threatening, or result in permanent impairment of a body 
function, or permanent damage to a body structure or necessitate medical 
(therapeutic) or surgical intervention to preclude permanent impairment of a body 
function or permanent damage to a body structure. 
Significant 
Adverse Event 
Those non-serious adverse events that occur with contact lens usage that are not 
sight-threatening but are usually symptomatic and may warrant therapeutic 
management and /or temporary or permanent discontinuation of contact lens wear. 
Non-Significant 
Adverse Events 
Those less severe non-serious adverse events that occur with contact lens usage 
that are not sight-threatening, may or may not be symptomatic and may warrant 
palliative management, such as ocular lubricants or  temporary interruption of contact 
lens wear. 
Unanticipated 
Adverse Device 
Effect 
Adverse events in a clinical trial that were not previously identified in the protocol in 
terms of nature, severity, or degree of incidence. An Unanticipated Serious Adverse 
Device Effect is an unanticipated adverse event that is serious in nature and caused 
by or associated with the device and is considered reportable. 

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Non-significant Adverse Events 
21 
Conjunctivitis (bacterial, viral or allergic) 
Notify ORE as 
soon as possible, 
within 5 working 
days;  
22 
Papillary conjunctivitis if ≥ mild scattered papillae/follicles approximately 1mm 
in diameter (e.g. ISO 11890 Grade 2), if 2 grade change from baseline 
23 
Asymptomatic corneal infiltrative events 
24 
Any sign and/or symptom for which temporary lens discontinuation for > 1 day 
is recommended (if not already classified) 
20 
Other sign and/or symptom warranting classification as a non-significant 
adverse event 
12.3.1.1 
NORMAL OR ADAPTIVE SYMPTOMS 
Transient symptoms such as end-of-day dryness, lens awareness, itching or burning or other 
discomfort may occur with contact lens wear and may occasionally reduce wearing time. These 
are not reported as adverse events unless in the investigator’s opinion they are 
unexpected in nature, severe or have a high rate of occurrence. 
12.3.2 PROCEDURES FOR ADVERSE EVENTS 
Treatment of an adverse event will depend on its nature and severity. Based on the clinical 
judgment of the investigator the participant may be referred to an ophthalmologist for treatment. 
The investigator will attempt to determine whether the reaction is related to the test device or a 
result of other factors. An Adverse Event Form (Appendix 8) will be completed for each adverse 
event. If both eyes are involved, a separate Adverse Event Form will be completed for each eye. 
Whenever possible, the adverse event will be photo-documented. 
Expenses incurred for medical treatment as part of study participation will be paid by the 
investigator (bills and prescription receipts kept). The participant must be followed until resolution 
and a written report completed indicating the subsequent treatment and resolution of the 
condition. 
12.3.2.1 
REPORTING ADVERSE EVENTS 
All potential Serious and Unanticipated Adverse Device Effects that are related or possibly 
related to participant participation will be reported to the Principal Investigator’s supervisor within 
24 hours of the investigator becoming aware of the event. The Principal Investigator will report 
the event to the ORE as soon as possible (by fax, mail/delivery, phone, or email) following the 
University of Waterloo Office of Research Ethics reporting guidelines.  All fatal or life threatening 
events will be reported immediately to the ORE. 

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Significant and Non-Significant Adverse Events will be reported to the ORE as soon as possible, 
but no later than 5 working days after the occurrence. 
13.4 PROTOCOL DEVIATIONS 
Protocol deviations are unanticipated or unintentional changes to a study made after it has 
received prior ethics clearance. Protocol deviations can be major or minor.  
12.4.1 MAJOR PROTOCOL DEVIATIONS 
Major protocol deviations may impact the research protocol, information consent document or 
other study materials, usually cannot be anticipated ahead of time and are often necessary to 
ensure the safety and welfare of the participants. 
The following are examples of protocol deviations that must be reported to the ORE: 
 
Changes in procedures initiated to eliminate immediate risks/hazards to participants; 
 
Enrollment of participants outside the protocol inclusion/exclusion criteria whether agreed 
to or not by the ethics committee; 
 
Inadvertent deviation in specific research intervention procedures or timing of the 
research intervention which could impact upon the safety or efficacy of the study-related 
intervention or upon the experimental design; 
 
Information consent documentation violations: no documentation of informed consent; 
incorrect version of, or incomplete, informed consent documentation used. 
12.4.2 MINOR PROTOCOL DEVIATIONS 
Protocol deviations caused by or which originate with research participants are considered 
minor, and normally are not reported to the ORE unless these result in increased risk to the 
participant(s). The following are examples of protocol deviations that are considered minor and 
do not require reporting to the ORE: 
 
Logistical or administrative aspects of the study (e.g., study participant missed 
appointment, change in appointment date); 
 
Inadvertent deviation in specific research intervention procedures or timing of the 
research intervention which would not impact upon the safety or efficacy of the study-
related intervention or upon the experimental design (i.e., missing a measurement during 
a session that is not considered critical for the study).  
 
 

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12.4.3 REPORTING AND DOCUMENTING PROTCOL DEVIATIONS 
Major protocol deviations must be reported to the ORE within 7 days of the deviation occurring 
(or its discovery) using the Protocol Deviation Report Form 107 (PDRF).  Information from the 
PDRF is provided to the Clinical Research Ethics Committee (CREC) at the next monthly 
meeting. 
All protocol deviations (major and minor) occurring during the study will be documented and 
included in the final report. 
13.5 PREMATURE TERMINATION OF THE STUDY 
The PI’s or the Office of Research Ethics at the University of Waterloo may terminate the study 
at any time for any reason. 
14 QUALITY ASSURANCE 
13.1 STUDY PARTICIPANT RECORDS 
Study participant records will be completed to comply with GCP guidelines. Records will contain: 
 
Study number; 
 
Participant ID; 
 
Date enrolled; 
 
Confirmation by lead investigator that participant meets eligibility criteria; 
 
Confirmation that participant received a signed and dated copy of informed consent; 
13.2 RETENTION OF STUDY RECORDS AND DATA 
Records and data from this study will be retained for a minimum of 25 years. Paper copies of 
study data will be safely held in a secure storage cabinet in a locked office at the School of 
Optometry and Vision Science, University of Waterloo and will be only available to personnel 
involved in the data collection of this study. The electronic research data will be encrypted as per 
Guidelines laid out by UW Information and Systems Technology and be stored on a password 
protected server held in a locked office at the School of Optometry and Vision Science.  The 
images we acquire, with all identifying information removed, will be kept on a secure password 
protected server stored in a locked office at the School of Optometry and Vision Science.  Image 
data will be saved using a coded file name associated with each participant, and the list of the 
participants' names and corresponding numbers will be stored in a separate file at UW. Access 
to electronic data, images, photographs and videos is limited to authorized study personnel. 

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Records will be confidentially disposed of in accordance with the guidelines laid out by the 
University of Waterloo.  More information regarding the University of Waterloo’s policies on 
information security is available on the following website: https://uwaterloo.ca/secretariat-
general-counsel/policies-procedures-guidelines/policy-8. 
14 CLINICAL TRIAL REGISTRATION 
Because this protocol is intended to test the early feasibility of the device and/or concept(s) 
being studied, it is not considered as an applicable clinical trial for clinical trials registry 
(www.ClinicalTrials.gov or equivalent). As such, this clinical trial will not be registered. 
15 REPORT 
A report will be generated within 4 weeks after the completion of the study for inclusion in the 
PI’s thesis. 
16  APPENDICES 
Appendix 1A and 1B Email recruitment script 
Appendix 2 Information consent letter 
Appendix 3 Screening/Fitting and Study Visit Form for GP Lenses 
Appendix 4 Biomicroscopy form 
Appendix 5 Ocular Symptom Questionnaire 
Appendix 6 Feedback and appreciation letter 
Appendix 7 Study Completion/Remuneration Form 
Appendix 8 Adverse Event Form (ORE) 
Appendix 9 Package Insert Boston XO Material 
Appendix 10 Fitting Guide for Custom Stable lenses 
17  REFERENCES 
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permeable scleral contact lens therapy in ocular surface disease. Am J Ophthalmol. 
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3.  
Walker MK, Bergmanson JP, Miller WL, Marsack JD, Johnson LA. Complications and 
fitting challenges associated with scleral contact lenses: A review. Contact Lens Anterior 

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Eye. British Contact Lens Association; 2015. 
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You J, Willcox MD, Madigan MC, Wasinger V, Schiller B, Walsh BJ, et al. Chapter Four – 
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