Femtosecond Laser-assisted Arcuate Incisions Versus Manual Arcuate Incisions Outcomes
Phase: NA
Conditions: Cataract
Sponsor: Gainesville Eye Associates

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Femtosecond laser-assisted arcuate incisions versus manual arcuate 
incisions outcomes 
An investigator initiated clinical trial 
1.  TITLE PAGE 
 
Protocol Number: 
CB-19-001 
Amendment Number 
Version 1.1 
IRB / ERC 
Salus IRB 
2111 West Braker Lane, Suite 400 
Austin, Texas 78758
 
Clayton Blehm, MD 
Gainesville Eye Associates 
2061 Beverly Rd 
Gainesville, GA 30501 
 
(funding only, this is an investigator-initiated study 
IIT # 50130883) 
Alcon (a Novartis Company) 
6201 South Freeway,  
Fort Worth, TX 76134-2099, USA  
 
Test Articles: 
LenSx laser arcuate relaxing incisions  
Manual (blade) arcuate relaxing incisions 
 
Investigators:  
 
Clayton Blehm, MD, Gainesville, GA 
 
 
 
 

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2.  GENERAL INFORMATION 
 
Objective 
To compare the effectiveness of LenSx laser arcuate relaxing 
incisions vs. manual (blade) arcuate relaxing incisions in patients 
with low, but significant, levels of astigmatism. 
Test Article(s)   
LenSx laser arcuate relaxing incisions 
 
Control Article(s) 
Manual (blade) arcuate relaxing incisions 
Sample size  
41 patients, 82 eyes  
Study Population 
Subjects ≥40 years of age presenting for astigmatism reduction at 
the time of cataract surgery or refractive lens exchange who are 
considered appropriate candidates for arcuate incisions.  
Number of sites 
One site (Gainesville, GA) 
Study Design 
A prospective, randomized, contralateral eye comparative study 
Masking 
None 
Variables 
Primary Endpoint:  
Residual refractive astigmatism 
Secondary Endpoint:  
Percentage of eyes with refractive astigmatism ≤ 0.50 D 
Uncorrected monocular distance visual acuity  
Corneal astigmatism at 3 months 
Manifest refraction at 3 months 
Exploratory Endpoints: 
Topographic changes 
 
Duration / Follow-up 
Pre-operative to 3 months post-operative 
 
 
Study will be registered with clinicaltrials.gov. 
 

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3.  TABLE OF CONTENTS 
1.  TITLE PAGE ............................................................................................................................... 1 
2.  GENERAL INFORMATION ......................................................................................................... 2 
3.  TABLE OF CONTENTS ............................................................................................................... 3 
4.  INTRODUCTION ....................................................................................................................... 5 
5.  OBJECTIVE(S)............................................................................................................................ 5 
6.  SUBJECTS ................................................................................................................................. 5 
6.1. Subject Population ....................................................................................................... 5 
6.2. Inclusion Criteria ........................................................................................................... 5 
6.3. Exclusion Criteria .......................................................................................................... 6 
6.4. Exclusion Criteria during surgery .................................................................................. 6 
7.  STUDY DESIGN ......................................................................................................................... 7 
7.1. Study Design ................................................................................................................. 7 
7.2. Methods Used to Minimize Bias ................................................................................... 7 
8.  STUDY PROCEDURE ................................................................................................................. 8 
8.1. Visits and Examinations ................................................................................................ 8 
8.2. Study Methods and Measurements ...........................................................................10 
8.3  Unscheduled Visits .....................................................................................................11 
8.4  Discontinued Subjects ................................................................................................11 
9.  ANALYSIS PLAN ......................................................................................................................12 
9.1. Analysis Data Sets .......................................................................................................12 
9.2. Statistical Methodology ..............................................................................................12 
9.3. General Statistical Considerations .............................................................................12 
10.  SAMPLE SIZE JUSTIFICATION ...............................................................................................12 
11. CONFIDENTIALITY/PUBLICATION OF THE STUDY .................................................................12 
12.  QUALITY COMPLAINTS AND ADVERSE EVENTS ...................................................................13 
12.1. General Information .................................................................................................13 
12.2. Monitoring for Adverse Events ................................................................................13 
12.3. Procedures for Recording and Reporting AEs and SAEs ...........................................13 
12.4. Follow-Up of Adverse Events and Quality Complaints .............................................16 

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13. GCP, ICH and ETHICAL CONSIDERATIONS ............................................................................16 
13.1 Confidentiality ...........................................................................................................16 
14.  STUDY PLAN .........................................................................................................................17 
 

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4.  INTRODUCTION 
Multiple options exist for the treatment of astigmatism at the time of cataract surgery.  
Many clinicians believe the residual refractive cylinder following cataract surgery should 
remain at 0.5D or less to achieve the most desirable visual outcomes. Patients with low 
levels of preoperative corneal astigmatism can opt for arcuate relaxing incisions. Manual 
(blade) arcuate relaxing incisions are in common use. More recently, laser arcuate 
incisions have been introduced with a promise of more predictable outcomes when 
compared to the manual technique.  
 
 5.  OBJECTIVE(S) 
The objective of this study is to compare the effectiveness of LenSx laser arcuate relaxing 
incisions vs. manual (blade) arcuate relaxing incisions in patients with low, but 
significant, levels of astigmatism. 
 
The primary outcome measure will be the residual refractive astigmatism. Secondary 
outcome measures will be the percentage of eyes with refractive astigmatism ≤ 0.50 D, 
uncorrected monocular distance visual acuity, corneal astigmatism and manifest 
refraction at 3 months. Exploratory endpoint will be the topographic changes. 
 
6.  SUBJECTS 
6.1. Subject Population  
Eligible test subjects will be patients presenting for astigmatism reduction at the time of 
cataract surgery or refractive lens exchange surgery who are interested and eligible for 
arcuate incisions. 
A total of 41 subjects at one site will be enrolled. Subjects must meet the inclusion 
criteria. Prior to enrollment, subjects will be provided information on the study and asked 
to sign a patient information and consent form to participate. The patient information and 
consent form will be approved by an appropriate ethics committee. 
6.2. Inclusion Criteria 
Subjects are eligible for the study if they meet the following criteria: 
Note: Ocular criteria must be met in both eyes. 
 are willing and able to understand and sign an informed consent;  
 are willing and able to attend all study visits; 
 are more than 40 years of age, of either gender and any race; 
 are presenting for cataract surgery or refractive lens exchange with a 
desire to reduce astigmatism and will be implanted with a non-toric lens  

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 have good ocular health, with no pathology that compromises visual 
acuity (outside of residual refractive error and cataract) 
 have 0.50D to 1.75D of regular corneal astigmatism 
 have potential acuity of 20/25 or better 
 Are scheduled to have a non-toric monofocal IOL (SN60WF) lens 
implanted in both eyes 
6.3. Exclusion Criteria 
If any of the following exclusion criteria are applicable to the subject or either eye, the 
subject should not be enrolled in the study. 
 Irregular astigmatism (e.g. keratoconus) 
 Corneal pathology (e.g. scar, dystrophy, pterygium, moderate-to-severe 
dry eye) 
 Monocular status (e.g. amblyopia) 
 Previous radial keratotomy, corneal refractive surgery or other corneal 
surgery (e.g. corneal transplant, DSAEK, lamellar keratoplasty) 
 Previous anterior or posterior chamber surgery (e.g., vitrectomy, laser 
iridotomy) 
 Diabetic retinopathy 
 Macular pathology (e.g. ARMD, ERM) 
 History of retinal detachment 
 Subjects who have an acute or chronic disease or illness that would 
confound the results of this investigation (e.g., immunocompromised, 
connective tissue disease, clinically significant atopic disease, diabetes, 
and any other such disease or illness), that are known to affect post-
operative visual acuity. 
 
Pregnancy has a known effect on the stability of refractions and visual acuity. As such, 
subjects who become pregnant during the study will not be discontinued but their data 
may be excluded from analyses of effectiveness. 
6.4. Exclusion Criteria during surgery  
If any of the following exclusion criteria are applicable to the study eye, the subject 
should not continue in the study.  
  
 If the laser arcuate procedure cannot be completed due to physiological or other 
considerations.  
 If there are complications related to completion of the arcuate incisions. 
 Other procedure, such as pupil stretch, expanders, iris hooks during surgery.    

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Note: Any subject in which surgery has been aborted for either eye should immediately 
be discontinued from the study and an exit form completed for that subject. These 
subjects will be followed up as per the clinic standard of care, monitored for safety, and 
their data will be excluded from the study efficacy analysis (obtained from FDA database 
Research Results Feb, 05, 2009). All adverse events will be appropriately documented 
and reported.  
 
Participants who are considered to be a vulnerable subject population will not be enrolled 
into the study. Vulnerable populations include, but are not limited to, the following:  
 
 Prisoners  
 Nursing home residents /institutionalized individuals  
 Mentally disabled /cognitively impaired individuals  
 Sponsor employees and their family members  
 Site employees and their family members that are directly and indirectly involved 
with the study  
 Economically and/or educationally disadvantaged individuals  
 Comatose individuals / traumatized individuals  
 Adults who do not read and/or write 
 Patients with deafness or severe hearing disability  
 Terminally ill individuals / individuals with life-threatening conditions 
 
7.  STUDY DESIGN 
7.1. Study Design  
This study is a comparative, prospective, randomized contralateral eye study of visual 
outcomes after LenSx laser arcuate relaxing incisions utilizing the Woodcock nomogram 
at 90% thickness vs. manual (blade) fixed keratome diamond knife at 600 microns for 
arcuate relaxing incisions utilizing the Donnenfeld nomogram. Subjects will be assessed 
pre-operatively and at 1 day, 1 month and 3 months post-operatively. Clinical evaluations 
will include measurement of visual acuity, manifest refraction and corneal astigmatism 
measurement with the Lenstar and slit lamp exam. 
 
The primary outcome measure will be the residual refractive astigmatism. Secondary 
outcome measures will be the percentage of eyes with refractive astigmatism ≤ 0.50 D, 
uncorrected monocular distance visual acuity, corneal astigmatism and manifest 
refraction at 3 months. Exploratory endpoint will be the topographic changes. 
 
7.2. Methods Used to Minimize Bias  
This is a contralateral eye study where one eye will be randomized to either the laser 
group or the manual group. This is expected to minimize patient bias.  

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The measurement of visual acuity will be conducted in a systematic fashion to minimize 
bias. Individuals conducting visual acuity measures will be instructed to perform the 
same testing in the same fashion for all subjects, with the same level of encouragement to 
subjects.  
 
All data collection will be completed through provided Case Report Forms (CRFs). All 
site personnel involved in the study will be trained in regard to conducting study-specific 
procedures. 
 
8.  STUDY PROCEDURE  
8.1. Visits and Examinations  
Subjects will participate in six study visits. Visits will include an uptake visit, one 
operative visits, and 3 postoperative visits (Visit numbers 3-5 below).  The visit schedule, 
complete with window and associated CRF forms, are displayed in Table 8.1-1.  Details 
of each study visit, including testing to be conducted, are provided below.   
 
 
Table 8.1-1.  Visit Schedule 
 
Visit 
Number
Visit Name 
Visit Window 
CRF 
Number
1 
Preoperative  
-30 to 0 days from surgery 
1 
2, 2A 
Operative 
0 from surgery 
2, 2A 
3, 3A 
1 Day Postoperative  
1-2 days postoperative 
3, 3A 
4 
1 Month Postoperative 
30 (±12) days postoperative* 
4 
5 
3 Months Postoperative 
90 (±20) days postoperative* 
5 
*From second eye surgery 
 
8.1.1. Preoperative  
 
At the preoperative exam, subjects will be consented, qualified for the study 
(compared with inclusion/exclusion criteria), and assigned a study ID/subject 
number.  Subject numbers will be assigned sequentially in the order of 
enrollment. Pre-operative qualification should take place no more than 30 days 
prior to surgery.   
 
A medical history will be taken and exams will include the tests described below: 
 manifest refraction, 
 visual acuity, 
 Corneal astigmatism measurements (Verion, Lenstar, topography),  
 Slit lamp exam, 

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In addition, all site-specific, routine preoperative measures should be undertaken.   
 
Measurements should be made as described in section 8.2 below.  
 
8.1.2. Operative (Surgery) 
 
All subjects will receive a Betadine prep in the usual sterile fashion. They will 
then be taken to the operative room and treated with the assigned method. Each 
patient would undergo a randomized process of one eye obtaining LenSx laser 
arcuate(s) and the contralateral eye obtaining manual blade arcuate(s).  Accepted 
nomograms would be utilized to calculate the exact length and positioning of the 
arcuate incisions.   
 
Outside of the femtosecond laser arcuate incisions, no other femtosecond 
procedure will be performed on any eyes. The corneal surgical incisions, 
capsulorhexis and fragmentation will be performed without use of the 
femtosecond laser system.  
 
All eyes will be implanted with a non-toric monofocal IOL, specifically the 
SN60WF lens (Alcon, Fort Worth, TX). 
 
Surgical findings will be recorded and any adverse events/serious adverse events 
(AEs/ SAEs) occurring during surgery will be noted at this visit. Any other 
problems during surgery and comments regarding surgery will be documented.  
Any subject whose surgery is not completed successfully will be documented in 
the appropriate case report form. These subjects will be monitored for safety but 
clinical performance data may be excluded from the analysis. 
Immediately following the laser treatment, the arcuate incisions will be opened at 
an operating microscope. All study subjects will be placed on an appropriate 
antibiotic and steroid drop QID for one week.  
For the following three weeks, only the steroid drop will be continued on a 
tapered dose. 
8.1.3. Postoperative 1 Day 
 
All routine postoperative measures should be undertaken.  In addition, the subject 
will undergo VA testing in accordance with the specifications below (Section 
8.2).  Adverse events will be monitored. 
 
8.1.4 Postoperative 1 Month 
 

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All routine postoperative measures should be undertaken.  In addition, the subject 
will undergo manifest refraction and VA testing in accordance with the 
specifications below (Section 8.2) and have their corneal astigmatism measured 
using the Lenstar, Verion and topography devices. Adverse events will be 
monitored. 
 
8.1.5. Postoperative 3 Months 
 
All routine postoperative measures should be undertaken.  In addition, the subject 
will undergo manifest refraction, VA testing, slit-lamp examination and corneal 
astigmatism measurements with the Lenstar, Verion and topography devices. 
Adverse events will be monitored. 
 
8.1.6. Exit Procedures 
 
In the event of premature exit from the study, all study related examinations 
should be completed where possible. The Exit CRF should be completed, noting 
that the subject did not complete the study and the reason for premature study 
exit.  If no premature exit from the study occurs, the Exit CRF should be 
completed at the end of Visit 5 (Postoperative 3 Months).  
 
8.2. Study Methods and Measurements 
All routine testing and basic eye examinations should be carried out at each study visit.  
Abnormalities should be recorded in the CRF “Comment” section.  Specific study 
examination procedures are outlined below.  
 
 
8.2.1. Manifest Refraction 
 
Perform a manifest refraction with a high contrast logMAR chart under photopic 
lighting conditions (>85 cd/m2).  Document refraction results with sphere, 
cylinder and axis readings.  If uncorrected visual acuity is not improved by 
manifest refraction, use zero for sphere and cylinder and draw a line through the 
blank for the axis.  
 
Note:  Each subject should be manually refracted to his/her best correction by an 
ophthalmologist, optometrist, or a skilled technician using a phoropter or trial 
lenses.   
 
 
8.2.2. Visual Acuity (VA) 
 
To obtain logMAR VA, ask subjects to begin reading the chart at the smallest row 
where all letters are easily distinguishable.  Have subjects continue to read rows 
with smaller letters and encourage subjects to guess at all letters in a line if at least 
one correct response was given on the previous row.  Request subjects read rows 

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until no letters on a row are read correctly or until all letters on a row are too 
indistinguishable to even be guessed.  
 
While the subject is reading the chart, record the number of letters on each line 
read incorrectly by the subject. The last line from which the subject read at least 
one letter correctly is recorded as the baseline logMAR VA.  The actual logMAR 
VA is calculated using the baseline logMAR VA line and the number of letters 
read incorrectly. This VA should be recorded as the best-corrected monocular 
visual acuity at distance. 
 
It is sufficient to record the uncorrected VA at distance for the 1-day visit. 
 
All visual acuity testing is performed monocularly. Postoperatively, conduct 
testing uncorrected at all visits. In addition, conduct testing with the manifest 
refraction in place at 1 and 3 months post-operatively.  
 
Distance VA 
Measure distance visual acuity using a high contrast logMAR ETDRS chart under 
photopic lighting (>85 cd/m2) at a distance of 4-6 m.   
 
8.2.3. Corneal astigmatism measurement 
 
This should be performed by an ophthalmologist, optometrist, or a skilled 
technician. The measurements will include use of the Lenstar device, the Atlas 
corneal topographer and the Verion imaging system. 
 
 
8.3  Unscheduled Visits 
Unscheduled exams may be conducted at the discretion of the Investigator with all 
relevant information from the exam recorded in the source documents and on the 
Unscheduled Visit pages within the CRF booklet. 
 
8.4  Discontinued Subjects 
Discontinued subjects are those who do not have an exit visit or who come into the office 
to be exited prior to the scheduled final study visit. Subjects may be discontinued from 
the study at any time if, in the opinion of the investigator, their continued participation in 
the study poses a risk to their health. The reasons for discontinuation include: 
a. Adverse event; 
b. Lost to follow-up; 
c. Subject decision unrelated to an adverse event; 
d. Protocol violation; 
e. Treatment failure; 
f. Other. 

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To ensure the safety of all subjects who discontinue prior to Visit 5, investigators should 
assess each subject and, if necessary, advise them of any therapies and/or medical 
procedures that might be needed to maintain their health. Any changes in medical health 
and/or use of concomitant medications also should be captured. 
 
9.  ANALYSIS PLAN 
9.1. Analysis Data Sets 
All subjects who are enrolled in the study will be evaluated for safety.  Efficacy analyses 
will be performed based on data from those eyes where uncomplicated LenSx or manual 
arcuate incisions were completed.   
9.2. Statistical Methodology 
A summary of the data will be prepared for all measurement time points.  Summaries of 
the changes observed between the pre-operative (baseline) and the 3 month post-
operative visits will also be summarized. Comparison of the laser and manual groups in 
terms of post-operative corneal astigmatism, uncorrected visual acuity and residual 
refractive cylinder and spherical equivalent refraction will be documented. 
 
For variables measured on a continuous scale, these summaries will include the sample 
size, as well as the mean, standard deviation, median, minimum, and maximum. These 
summaries will be provided for all eyes completing the study. 
 
9.2.1. Within-treatment Changes 
For variables measured on a continuous scale, the statistical significance of 
within-treatment changes between time points will be investigated using paired t-
tests.  For variables measured on an ordinal categorical scale, the Wilcoxon 
signed-rank test will be employed. 
9.3. General Statistical Considerations 
The statistical analyses will be performed using Statistica, version 12 or higher.  Any 
statistical tests of hypotheses will employ a level of significance of alpha=0.05. 
 
10.  SAMPLE SIZE JUSTIFICATION 
The sample size [based on a power of 0.8, an alpha of 0.05, an estimated standard 
deviation of postoperative refractive astigmatism of 0.4D (from the literature) and an 
expected improvement on average of 0.25D with laser incisions] would be 41 subjects. 
11. CONFIDENTIALITY/PUBLICATION OF THE STUDY 
The existence of this Study is confidential and should not be discussed with persons 
outside of the Study.  Results will be submitted for publication and presentation at 
national and/or international meetings. A manuscript will be submitted to peer-review 
journals for publication but there is no guarantee of acceptance. 

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12.  QUALITY COMPLAINTS AND ADVERSE EVENTS 
All subjects will be monitored for adverse events over the course of the study. A place to 
record any adverse event is included on each case report form. 
12.1. General Information 
An Adverse Event (AE) is any untoward medical occurrence in a subject who is 
administered. a study treatment regardless of whether or not the event has a causal 
relationship with the treatment. An AE, therefore, can be any unfavorable or unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the study treatment, whether or not related to the treatment. In clinical 
studies, an AE can include an untoward medical occurrence occurring at any time, 
including run-in or washout periods, even if no study treatment has been administered. 
12.2. Monitoring for Adverse Events 
At each visit, after the subject has had the opportunity to spontaneously mention any 
problems, the Investigator should inquire about AEs by asking if the patient has any 
problems.  
12.3. Procedures for Recording and Reporting AEs and SAEs 
Subsequent to signing an informed consent form, all untoward medical occurrences that 
occur during the course of the study must be documented on an Adverse Event Form 
(AEF). A separate AEF must be filled out for each event. When possible, signs and 
symptoms indicating a common underlying pathology should be documented as one 
comprehensive event. For each recorded event, the AE documentation must include the 
onset date, outcome, resolution date (if event is resolved), intensity (ie, severity), any 
action with study treatment taken as a result of the event, and an assessment of the 
adverse event’s relationship to the study treatment. 
Nonserious Adverse Events 
A nonserious AE is defined as any untoward change in a subject's medical health that 
does not meet serious criteria noted below (eg, is not life-threatening, does not require 
hospitalization, does not prolong a current hospitalization, is not disabling, etc.). All 
adverse events must be reported regardless of whether or not they are related to the study 
treatment. 
 
For non-serious adverse events, an AEF containing all available information will be 
collected on a routine basis and submitted to the Medical Monitor at the close of the 
study.  
 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any adverse experience that meets any of the 
following criteria: 
• 
Results in death. 
• 
Is life-threatening. 

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NOTE: Life-threatening means that the subject was at immediate risk of death 
from the reaction as it occurred, ie, it does not include a reaction which 
hypothetically might have caused death had it occurred in a more severe form. 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
NOTE: In general, hospitalization signifies that the individual remained at the 
hospital or emergency ward for observation and/or treatment (usually involving 
an overnight stay) that would not have been appropriate in the physician's office 
or an out-patient setting. Complications that occur during hospitalization are AEs. 
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred, the 
event should be considered serious. 
• 
Results in persistent or significant disability/incapacity. Disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions. 
NOTE: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza, or accidental trauma (eg, 
sprained ankle) which may interfere or prevent everyday life functions but do not 
constitute a substantial disruption. 
• 
Is an important medical event. An important medical event is an event that may not 
result in death, be life-threatening, or require hospitalization but may be considered 
an SAE when, based upon appropriate medical judgment, it may jeopardize the 
subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in the definitions for SAEs. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in subject hospitalization, or 
the development of drug dependency or drug abuse. 
All available information on a serious adverse event(s) and any other associated AE, 
if applicable, must be forwarded to the study coordinator for forwarding to the 
Medical Monitor immediately (ie, within one working day of the Investigator’s or 
site’s knowledge of the event) as follows: 
o In studies utilizing EDC (electronic data capture), all available information for 
the SAE and any associated AE(s) must be entered immediately into the EDC 
system.  
o Additional information for any applicable event is to be reported as soon as it 
becomes available. 
 
In addition to the reporting of serious adverse events to the study Medical Monitor, the 
SAE must be reported to the IRB / IEC according to their requirements. 
 
The investigator must document all adverse events related to the procedure (serious and 
non-serious but related) and all serious adverse events (related and unrelated) on the 
Adverse Procedure Effect and Serious Adverse Event Form. Any procedure-related 
quality complaints will also be documented.  
 

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 Both the Quality Complaint Form and the Adverse Procedure Effect and 
Serious Adverse Event Form must be faxed immediately to the study 
coordinator using the contact information below. Additional relevant 
information is to be reported as soon as it becomes available.   
Study Coordinator Contact Information for Prospective Laser vs Manual Arcuate 
Incision Outcome Study 
Study Staff 
Business Phone 
Business email 
Home Phone 
MaryAnn Thomas 
770-532-4444 
mthomas@gainesvilleeye.com 
770-519-2099 
 
Further, depending upon the nature of the adverse event (serious or non-serious) or 
quality complaint being reported, the study sponsor may request copies of applicable 
portions of the subject’s medical records.  The investigator must also report all adverse 
events and quality complaints according to the relevant IRB requirements. 
 
 
12.3.1 Intensity and Causality Assessments  
For every adverse event and quality complaint, the investigator must assess the 
causality as Related or Not Related to the medical procedure under investigation. 
An assessment of causality will also be performed by the Medical Monitor 
utilizing the same definitions, as shown below: 
 
Causality 
Related 
An adverse event or quality complaint classified as related may be 
either definitely related or possibly related where a direct cause 
and effect relationship with the medical procedure has not been 
demonstrated, but there is a reasonable possibility that the adverse 
event or quality complaint was caused by the medical procedure. 
 
 
Not Related 
An adverse event or quality complaint classified as not related may 
either be definitely unrelated or simply unlikely to be related (i.e., 
there are other more likely causes for the adverse event or quality 
complaint). 
 
Where appropriate, the investigator must assess the intensity (severity) of the 
adverse event as mild, moderate, or severe based on medical judgment with 
consideration of any subjective symptom(s), as defined below:  
 
Intensity (Severity) 
Mild 
An adverse event is mild if the subject is aware of but can easily 
tolerate the sign or symptom. 

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Moderate 
An adverse event is moderate if the sign or symptom results in 
discomfort significant enough to cause interference with the 
subject’s usual activities. 
Severe 
An adverse event is severe if the sign or symptom is incapacitating 
and results in the subject’s inability to work or engage in their 
usual activities. 
 
The investigator must document any action taken (i.e., medication, intervention, 
or treatment plan) and outcome of the adverse event or quality complaint when 
applicable. 
 
12.4. Follow-Up of Adverse Events and Quality Complaints 
The investigator is responsible for adequate and safe medical care of subjects during the 
study and for ensuring that appropriate medical care and relevant follow-up procedures 
are maintained after the study.  Any additional data from these follow-up procedures 
must be documented and available to the study coordinator who, with the Medical 
Monitor, will determine when the data need to be documented on the CRFs.  
 
13. GCP, ICH and ETHICAL CONSIDERATIONS 
This study will be conducted in compliance with Good Clinical Practices (GCPs), 
including International Harmonization (ICH) Guidelines, and in general, consistent with 
the 1996 version of the Declaration of Helsinki.  In addition, all applicable local, state 
and federal requirements will be adhered to.  
 
This study is to be conducted in accordance with Institutional Review Board regulations.  
The investigator will obtain appropriate IRB/ethics committee approval prior to initiating 
the study. 
13.1 Confidentiality 
The data collected will be data typical for the procedure(s) when performed on eyes 
outside the study. Any data collected will become part of the patient’s clinical record. 
The data will be subject to the same privacy and confidentiality as other data in the 
clinical record. 
 
Only the principal investigator, research consultant and clinic staff will have access to the 
data collected. All data shared outside the practice will be de-identified; patients’ 
protected health information will not be available and will not be reported in any analyses 
or publications. No data will be sold to third parties. De-identified data may be used for 
future research.  
 
 
 

Femtosecond laser vs manual arcuate incision Protocol 
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14.  STUDY PLAN  
Table 14.-1. Study Plan 
Activity 
Preoperative 
Operative 
Postoperative 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
 
 
1 Day 
1 Month 
3 Month 
Informed Consent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
General Information:   
Medical History 
X 
 
 
 
 
Surgery 
 
X 
 
 
 
Manifest Refraction 
X 
 
 
X 
X 
Uncorrected Distance VA 
X 
 
X 
X 
X 
Corrected Distance VA 
X 
 
 
X 
X 
Corneal astigmatism measurement 
X 
 
 
X 
X 
Monitor for Adverse Events 
 
X 
X 
X 
X 
Complete Exit Form1 
 
 
 
 
X 
 
1 Complete Exit Form upon termination of subject participation, or at Visit 5, whichever 
occurs first.