Comparison of Visual Outcomes With Mini-Monovision Between a Monofocal and an Adjustable Intraocular Lens
Conditions: Cataract
Sponsor: Gainesville Eye Associates

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Comparison of Visual Outcomes with Mini-Monovision between a 
Monofocal and an Adjustable Intraocular Lens  
An investigator-initiated clinical trial 
1.  TITLE PAGE 
 
Protocol Number: 
CB-23-02  
Amendment Number 
Version 1.0 
IRB / ERC 
Salus IRB 
2111 West Braker Lane, Suite 400 
Austin, Texas 78758 
 
 
Sponsor Name & Address: 
Clayton Blehm, MD 
North Georgia Eye Associates 
2061 Beverly Rd Gainesville, GA 30501 
 
(funding only, this is an investigator-initiated study 
IIT # 89850521) 
Alcon  
6201 South Freeway,  
Fort Worth, TX 76134-2099, USA  
 
 
Test Articles: 
The Clareon™ Monofocal Intraocular Lens  
(Toric and Non-Toric) 
The Light-Adjustable Lens™ 
 
  Investigator:  
 
  Clayton Blehm, MD 
 
 
 
 
 
 
 

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2 . INVESTIGATOR AGREEMENT 
 
I confirm that I have read and that I understand this protocol entitled “Comparison 
of Visual Outcomes with Mini-Monovision between a Monofocal and an Adjustable 
Intraocular Lens”, and understand the use of the study products. I agree to conduct 
this study in accordance with the requirements of this protocol and also protect the 
rights, safety, privacy, and well-being of study subjects in accordance with the 
following: 
 
• 
The ethical principles that have their origin in the Declaration of Helsinki. 
• 
All applicable laws and regulations, including, without limitation, data privacy 
laws and regulations. 
• 
Regulatory requirements for reporting serious adverse events defined in Section 
13 of this protocol. 
 
 
 
 
Signature of Investigator  (Date) 
 
Investigator Name (print or type) 
 
Investigator’s Title 
 
Name of Facility 
 
Location of Facility (City) 

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3.  GENERAL INFORMATION 
 
Objective 
To compare binocular visual outcomes with light adjustable lens 
(LAL) vs. Clareon monofocal/toric IOL when both are targeting 
mini-monovision (-0.75 ~ -1.00 D in the non-dominant eye).  
 
The hypothesis is that the Clareon monofocal/toric IOL with 
mini-monovision will provide non-inferior binocular distance 
vision compared to LAL mini-monovision (non-inferiority 
margin: 0.1 logMAR). 
 
Test Article(s)   
The Clareon™ Monofocal Intraocular Lens (Toric and Non-Toric) 
The Light-Adjustable Lens™ 
 
Sample size  
138 subjects total (69 in each group) 
Study Population 
Age-related Cataract patients with ≥ 0.75D corneal astigmatism 
and without previous experience of monovision > -1.00D offset. 
 
Number of sites 
One 
Study Design 
Single center, multi-surgeon, prospective, randomized, 
comparative study. 
 
Masking 
None. 
 
Variables 
Primary:  Binocular corrected distance visual acuity (CDVA), 3-
months postop. 
 
Secondary: 
• Binocular uncorrected distance visual acuity (UDVA), 3-
months postop.  
• Binocular distance-corrected intermediate visual acuity 
(DCIVA) at 66cm, 3-months postop.  
• Binocular uncorrected intermediate visual acuity (UIVA) 
at 66cm, 3-months postop. 
• Monocular corrected distance visual acuity (CDVA), 3-
months postop.  

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• Monocular uncorrected distance visual acuity (UDVA), 3-
months postop.  
• Monocular distance-corrected intermediate visual acuity 
(DCIVA) at 66cm, 3-months postop.  
• Monocular uncorrected intermediate visual acuity (UIVA) 
at 66cm, 3-months postop. 
Exploratory: 
• Binocular distance-corrected near visual acuity (DCNVA) 
at 40cm, 3-months postop.  
• Binocular uncorrected near visual acuity (UNVA) at 
40cm, 3-months postop. 
• Monocular distance corrected defocus curve at 3 months 
post-op for both eyes in LAL group and dominant eye for 
Clareon group. 
• Binocular defocus curve at 3 months post-op (dominant 
eye: plano corrected, non-dominant: -1.00D)  
• Manifest refraction (MRSE, residual sphere, and residual 
astigmatism) at postoperative day 17-28 and at 3 months 
post-op. 
• Patient reported spectacle usage questionnaire (PRSIQ) at 
postoperative day 17-28 and at 3 months post-op 
• Total ocular, corneal and internal HOA and SA with 
iTRACE for both eyes in LAL group and dominant eye 
for Clareon group (Objective depth of focus measurement 
with iTRACE for each eyes in both groups) 
• Number of days and post-op office visits from cataract 
surgery to routine "release of care visit” (i.e. final lock-in 
for LAL group, 17-28 days after 2nd eye surgery for 
Clareon group). 
 

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Duration / Follow-up 
Preoperative to 3 months postoperative  
 
 
 
The study will be registered with clinicaltrials.gov.  
 
 
The study will be conducted in compliance with the protocol, GCP and applicable 
regulatory requirements 
 

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4.  TABLE OF CONTENTS 
1.  TITLE PAGE .............................................................................................................................. 1 
2 . INVESTIGATOR AGREEMENT .................................................................................................. 2 
3.  GENERAL INFORMATION ........................................................................................................ 3 
4.  TABLE OF CONTENTS .............................................................................................................. 6 
5.  INTRODUCTION ...................................................................................................................... 8 
6.  OBJECTIVE(S) .......................................................................................................................... 8 
7.  SUBJECTS ................................................................................................................................ 8 
7.1. Subject Population ...................................................................................................... 8 
7.2. Inclusion Criteria ......................................................................................................... 8 
7.3. Exclusion Criteria ......................................................................................................... 9 
8.  STUDY DESIGN ........................................................................................................................ 9 
8.1. Study Design ................................................................................................................ 9 
8.2. Methods Used to Minimize Bias ................................................................................ 10 
9.  STUDY PROCEDURE .............................................................................................................. 11 
9.1. Informed Consent / Subject enrollment ................................................................... 11 
9.2. Visits and Examinations ............................................................................................. 11 
9.3. Study Methods and Measurements .......................................................................... 13 
9.4.  Unscheduled Visits ................................................................................................... 15 
9.5.  Discontinued Subjects .............................................................................................. 15 
10.  ANALYSIS PLAN ................................................................................................................... 15 
10.1. Analysis Data Sets .................................................................................................... 15 
10.2. Statistical Methodology .......................................................................................... 15 
10.3. General Statistical Considerations .......................................................................... 16 
11.  SAMPLE SIZE JUSTIFICATION .............................................................................................. 16 
12. CONFIDENTIALITY/PUBLICATION OF THE STUDY ................................................................ 16 
13.  QUALITY COMPLAINTS AND ADVERSE EVENTS .................................................................. 17 
13.1. General Information ................................................................................................ 17 
13.2. Monitoring for Adverse Events ............................................................................... 17 
13.3. Procedures for Recording and Reporting AEs and SAEs .......................................... 17 
13.4. Follow-Up of Adverse Events and Quality Complaints ............................................ 20 

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13.5. Safety Analyses ........................................................................................................ 20 
14. GCP, ICH and ETHICAL CONSIDERATIONS ........................................................................... 20 
14.1 Confidentiality .......................................................................................................... 21 
15.  STANDARD EVALUATION PROCEDURES ............................................................................. 22 
Table 15.1. Proposed Visits and Study Assessments ........................................................ 22 
16. DATA CONFIDENTIALITY ...................................................................................................... 23 
17. FINANCIAL AND INSURANCE INFORMATION/STUDY RELATED INJURIES ............................ 23 
18. STUDY ENDPOINT CRITERIA ................................................................................................ 23 
18.1. Patient Completion of Study ................................................................................... 23 
18.2. Patient Discontinuation ........................................................................................... 23 
18.3. Patient Termination ................................................................................................ 23 
18.4. Study Termination ................................................................................................... 24 
18.5. Study Completion .................................................................................................... 24 
19. SUMMARY OF RISKS AND BENEFITS .................................................................................... 24 
19.1. Summary of risks ..................................................................................................... 24 
19.2. Summary of benefits ............................................................................................... 24 
REFERENCES .............................................................................................................................. 24 
 
 
 

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5.  INTRODUCTION 
The Light Adjustable Lens (LAL) is claimed to be the first and only intraocular lens 
(IOL) that can be customized to patient's satisfaction after cataract and IOL implantation 
surgery by using UV light treatments to adjust the refractive and visual outcomes. LAL 
allows cataract patients, even those without monovision experience to try mini-
monovision and adjust to their visual satisfaction to provide improved range of vision. 
Clinically, monovision or mini-monovision with monofocal IOLs has been used to 
provide some presbyopia mitigation, especially before the invention of modern multifocal 
and extended depth of focus IOLs. 
 
There is limited data on the visual outcomes for patients with mini-monovision with 
Light Adjustable Lens (LAL) compared to mini-monovision with a 
traditional monofocal/toric IOL. Previous studies have shown that the Clareon® 
intraocular lens (IOL) (Alcon, Fort Worth, Texas, USA) provides good visual outcomes 
for patients at distance.1 The purpose of this study is to compare binocular visual 
outcomes with LAL vs. Clareon monofocal/toric IOL when targeting mini-monovision (-
0.75 ~ -1.00D).  
6.  OBJECTIVE(S) 
To compare binocular visual outcomes with LAL vs. Clareon monofocal/toric IOL when 
targeting mini-monovision (-0.75 ~ -1.00D).   
7.  SUBJECTS 
7.1. Subject Population  
Eligible test subjects will be adult normal astigmatic (≥ 0.75D corneal astigmatism) 
cataract patients presenting for cataract surgery who are considered appropriate 
candidates for intraocular lens implantation.  
 
A total of 138 subjects at one site will be enrolled (69 per group). Both eyes of a subject 
must 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. 
7.2. Inclusion Criteria 
Subjects are eligible for the study if they meet the following criteria: 
Note: Ocular criteria must be met in both eyes. 
• Adult patients undergoing age-related cataract surgery with expected best-
corrected visual outcomes of 20/25 or better 
• Regular corneal astigmatism of 0.75D-2.50D 
• Dilated pupil diameter of 7mm or greater 

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7.3. 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. 
• Moderate-severe corneal pathology, irregular astigmatism, preexisting 
macular disease and other retinal degenerative diseases that is expected to cause 
future vision loss, glaucoma, severe dry eye disease, history of uveitis, 
ocular herpes simplex virus, nystagmus, strabismus, zonular laxity or dehiscence, 
pseudoexfoliation. 
• History of corneal refractive and intraocular surgery. 
• Patients taking systemic medication that may increase sensitivity to UV light or 
that may cause toxicity to the retina. 
The principal investigator reserves the right to declare a patient ineligible or non-
evaluable based on medical evidence that indicates they are unsuitable for the trial.  
 
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. 
8.  STUDY DESIGN 
8.1. Study Design  
This study is a single center, multi-surgeon, prospective, randomized, comparative study 
of binocular corrected distance visual acuity (CDVA) after successful bilateral cataract 
surgery. Subjects will be assessed pre-operatively, operatively and at up to 6 post-
operative visits. Clinical evaluations will include administration of patient reported 
spectacle usage questionnaire (PRSIQ), as well as measurement of monocular and 
binocular visual acuities at distance, intermediate, and near, defocus curve, manifest 
refraction, measurement of higher order aberrations. 
 
The primary outcome measure will be the binocular corrected distance visual acuity 
(CDVA), 3-months postop. 
 
Secondary outcome measures are as follows: 
• Binocular uncorrected distance visual acuity (UDVA), 3-months postop.  
• Binocular distance-corrected intermediate visual acuity (DCIVA) at 66cm, 3-
months postop.  
• Binocular uncorrected intermediate visual acuity (UIVA) at 66cm, 3-months 
postop. 
• Monocular corrected distance visual acuity (CDVA), 3-months postop.  
• Monocular uncorrected distance visual acuity (UDVA), 3-months postop.  

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• Monocular distance-corrected intermediate visual acuity (DCIVA) at 66cm, 3-
months postop.  
• Monocular uncorrected intermediate visual acuity (UIVA) at 66cm, 3-months 
postop. 
Exploratory outcome measures are as follows: 
• Binocular distance-corrected near visual acuity (DCNVA) at 40cm, 3-months 
postop.  
• Binocular uncorrected near visual acuity (UNVA) at 40cm, 3-months postop. 
• Monocular distance corrected defocus curve at 3 months post-op for both eyes in 
LAL group and dominant eye for Clareon group. 
• Binocular defocus curve at 3 months post-op (dominant eye: plano corrected, non-
dominant: -1.00D)  
• Manifest refraction (MRSE, residual sphere, and residual astigmatism) at 
postoperative day 17-28 and at 3 months post-op. 
• Patient reported spectacle usage questionnaire (PRSIQ) at postoperative day 17-28 
and at 3 months post-op 
• Total ocular, corneal and internal HOA and SA with iTRACE for both eyes in 
LAL group and dominant eye for Clareon group (Objective depth of focus 
measurement with iTRACE for each eyes in both groups). 
• Number of days and post-op office visits from cataract surgery to routine "release 
of care visit” (i.e. final lock-in for LAL group, 17-28 days after 2nd eye surgery 
for Clareon group). 
8.2. Methods Used to Minimize Bias  
Patient selection will be based on the patient’s interest and the surgeon’s opinion as to 
whether they are a suitable candidate for IOL implantation. Subjects will be randomized 
to treatment groups.  
 
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. Questionnaire instructions will be provided to all patients in a similar manner.  
 
 

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All data collection will be completed through provided Case Report Forms (CRFs) or 
computer files generated by automated test equipment. All site personnel involved in the 
study will be trained in regard to conducting study-specific procedures. 
8.3. Method of Assigning Subjects to Treatment Arms 
Subjects will be assigned to the Clareon monofocal or the LAL treatment groups in a 1:1 
ratio using the method of randomly permuted blocks.  
9.  STUDY PROCEDURE  
9.1. Informed Consent / Subject enrollment  
No subject will be enrolled into the study who does not meet the inclusion/exclusion 
criteria and does not sign the current approved informed consent document. Informed 
consent will be obtained prior to collecting any data for the study. The original signed 
documents will be maintained by the investigator as a permanent part of the subject's 
medical records. A signed copy will be provided to the subject.   
9.2. Visits and Examinations  
Subjects will participate in eight study visits, one eye per visit for bilateral surgery. Visits 
will include an uptake visit, two operative visits, and up to 6 total postoperative visits 
(Visit numbers 1-8 below).  The visit schedule, complete with window and associated 
CRF forms, are displayed in Table 9.2-1.  Details of each study visit, including testing to 
be conducted, are provided below.   
 
Table 9.2-1.  Visit Schedule 
 
Visit 
Number 
Visit Name 
Visit Window 
Group 
CRF 
Number 
1 
Preoperative  
-90 to 0 days from surgery 
L,C 
1 
2,2a 
Operative 
0 from surgery 
L,C 
2,2a 
3 
Follow Up Visit and LAL with UV 
treatment #1 
POD 17-28  
L,C 
3 
4 
LAL with UV treatment #2 or 
lock-in #1 
POD 24-42 
L 
4 
5 
 LAL with UV treatment #3 or 
lock-in #1 or lock-in #2 
POD 31-56  
L 
5 
6 
 LAL with lock-in #1 or LAL lock-
in #2 (if needed)* 
POD 38-63  
L 
6 
7 
LAL with lock-in #2 (if needed)* 
POD 45-70  
L 
7 
8 
Final Visit 
POD 90 ± 14 days 
L,C 
8 
C = Clareon Group; L = LAL Group; POD = postoperative day 
*Note that visits 6 and 7 may not be necessary as not all subjects need 3 UV treatments, 
but each subjects will need 2 lock-ins.  
 
9.2.1. Preoperative  
 

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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 at each site in the order of 
enrollment. Pre-operative qualification should take place no more than 90 days 
prior to surgery.   
 
A medical history will be taken and exams will include the tests described below: 
§ manifest refraction, 
§ visual acuity  
 
In addition, all site-specific, routine, usual standard of care preoperative measures 
should be undertaken.   
 
Measurements should be made as described in section 9.3 below.  
 
9.2.2. Operative (Surgery) 
 
All subjects will undergo cataract surgery with implantation of either the Clareon 
or LAL IOL. The surgeon’s usual standard of care with regard to treatment and 
medication will be used for all study subjects.  
 
All patients will undergo bilateral femtosecond laser assisted cataract surgery 
(with ORA in the Clareon group). Surgeries will be completed 1 week apart with 
the non-dominant eye being the first eye. Surgeries will include femtosecond laser 
arcuate keratotomy or Clareon monofocal/toric IOL power calculation targeting 
(dominant eye: Plano ± 0.25D; non-dominant eye: -0.75 ~ -1.00D). Personalized 
lens constants for Clareon and Clareon toric will be used with Barrett Universal II 
formula, Barrett toric calculator and will consider the results from Hill RBF. If 
discrepancy between ORA and Barrett Universal II, will adjust to first minus on 
sphere that ORA recommends and will adjust one T power up or down based on 
ORA. 
 
LAL patients will have a pre-op target of closest to +0.25D calculated with the 
Barrett Universal II formula. LAL patients will undergo UV treatment until 
targeted refractive outcomes are achieved (dominant eye: plano ± 0.25D; non-
dominant eye: -0.75 ~ -1.00D). 
 
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. 

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9.2.3. Postoperative Day 17 to 28 
All routine, usual standard of care postoperative measures should be undertaken.  
In addition, the subject will undergo VA, manifest refraction, PRSIQ 
questionnaire, and iTrace testing in accordance with the specifications below 
(Section 9.3).  Adverse events will be monitored. 
 
9.2.4. Postoperative UV Treatments 
LAL patients will undergo UV treatment until targeted refractive outcomes are 
achieved (dominant eye: plano ± 0.25D; non-dominant eye: -0.75 ~ -1.00D). All 
routine, usual standard of care postoperative measures should be undertaken.  In 
addition, the subject will undergo VA, manifest refraction, and iTrace testing 
(Section 9.3) at these visits. Any device deficiencies or adverse events will be 
monitored. 
 
9.2.5. Postoperative Day 90 
All routine, usual standard of care postoperative measures should be undertaken.  
In addition, the subject will undergo VA, manifest refraction, defocus curve, 
PRSIQ questionnaire, and iTrace testing (Section 9.3). Any device deficiencies or 
adverse events will be monitored. 
 
9.2.6. 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 7 (Postoperative Day 90).  
 
9.3. 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.  
 
 
9.3.1. 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.   
 
 
9.3.2. Visual Acuity (VA) 

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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 
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.  
 
Distance VA 
Measure distance visual acuity using a high contrast logMAR ETDRS chart under 
photopic lighting (>85 cd/m2) at a distance of 4 m.   
 
Intermediate VA 
Have the subject view an appropriately-scaled high-contrast logMAR ETDRS 
Visual Acuity Chart at 66 cm. Visual acuity determined with the chart will be 
recorded and scored.  
 
Near VA 
Have the subject view an appropriately-scaled high-contrast logMAR ETDRS 
Visual Acuity Chart at 40 cm. Visual acuity determined with the chart will be 
recorded and scored.  
 
9.3.3 Defocus Curve 
Perform monocular distance corrected (corrected to plano) and binocular defocus 
curve (dominant eye: plano corrected, non-dominant: -1.00) with a high contrast 
logMAR chart under photopic lighting conditions (>85 cd/m2). Conduct testing 
with the manifest distance refraction in place in a phoropter. Add an over-
correction of +1.0 D and record VA. Reduce the correction by +0.5 D and retest 
and record VA. Reduce the correction by +0.25 D and retest and record VA. Add 
an over-correction of -2.50 D and record VA. Remove over-correction in 0.5 D 
increments while testing VA at each step (also be sure to record the VA at -0.25 
D). The procedure ends with VA testing at a 0.0 D over-correction (best-corrected 
distance refraction).  
 
9.3.3 Questionnaires 
The Patient reported spectacle usage questionnaire (PRSIQ) will be administered 
to subjects. The administrator should ensure the subjects understand the nature of 
the questions but should not interpret them for the subject. 

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9.4.  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. 
9.5.  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. 
To ensure the safety of all subjects who discontinue prior to Visit 8, 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 should also be captured. 
10.  ANALYSIS PLAN 
10.1. 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 cataract surgery 
with IOL implantation was completed.   
10.2. Statistical Methodology 
A summary of the data will be prepared for all measurement time points.   
 
10.2.1. Within-treatment Changes 
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. For variables measured on a categorical scale, summaries will provide 
the number and percentage of eyes in each category. These summaries will be 
provided for all eyes completing the study.  
 
Differences between parametric variables will be compared using a two-sample t-
test. Differences between categorical variables will be compared using the 2-
sample test for equality of proportions.  
 
For non-inferiority testing, if the upper boundary of the 95th confidence interval 
is not greater than 0.1 logMAR, non-inferiority will be claimed.  
 

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The step-down methodology will be used on the non-inferiority endpoints in the 
following order: 
1) Binocular CDVA 
2) Binocular DCIVA 
3) Binocular UDVA 
4) Binocular UIVA 
 
The correlation of total ocular and internal HOAs (especially SA) with monocular 
DCIVA will be evaluated using regression modelling. Findings from these models 
will provide an indication of whether any HOAs are statistically significantly 
associated with post-op DCIVA, and the strength of any such association. 
10.3. General Statistical Considerations 
The statistical analyses will be performed using R, version 4.2.2 or higher.  Any 
statistical tests of hypotheses will employ a level of significance of alpha=0.05. 
11.  SAMPLE SIZE JUSTIFICATION 
Assuming a difference in mean visual acuity between groups of 0.05 logMAR2 and a 
pooled standard deviation of 0.1 logMAR, the study would require a sample size of: 69 
subjects for each group (total sample size of 138 subjects), to achieve a power of 90% 
and alpha = 0.05. 
 
There is significant uncertainty in the assumptions for mean difference between groups 
and pooled standard deviation. Therefore, blinded sample size re-estimation is planned. 
One interim analysis will be conducted after enrollment of 30 subjects in each group (60 
subjects total) to re-estimate the sample size.  
 
One interim analysis will look at the variability in each group (biostatistician should be 
blinded to the groups). Using these values, the required sample size will be re-estimated. 
12. 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. 
 
All study data will be collected on appropriate Case Report Forms (CRFs). No protected 
health information will be included on the forms. CRFs will be retained in the patient’s 
file for a minimum period of 3 years. Collected information will only be used for 
purposes of this study and no information will be sold to third parties. The following 
people will have access to your study records: 
 
•    Study Doctor and staff involved with the study 
 
•    Study Monitor or Auditor 

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•    Sponsor Company or Research Institution 
 
•    Review boards or accrediting agencies 
 
•    Other State or Federal Regulatory Agencies 
 
The de-identified data may be shared with other researchers for future analysis. 
13.  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. 
13.1. 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. 
13.2. 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.  
13.3. 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 (i.e., 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 (e.g., 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. 
 

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For nonserious 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. 
NOTE: Life-threatening means that the subject was at immediate risk of death 
from the reaction as it occurred; i.e., 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 (e.g., 
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 (i.e., 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. 
 

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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 device events (serious and nonserious but 
related) and all serious adverse events (related and unrelated) on the Adverse Device 
Effect and Serious Adverse Event Form. Any device quality complaints will also be 
documented.  
 
• Both the Quality Complaint Form and the Adverse Device Effect and Serious 
Adverse Event Form must be e-mailed immediately to the study coordinator. 
• Additional relevant information is to be reported as soon as it becomes 
available.   
 
Study coordinator contact information is provided below. 
 
Table 13.3.-1:  
Contact Information for the Study 
Study Staff 
(Coordinator) 
Business Phone 
e-mail 
24-hour  
Office Phone 
Maryann Thomas 
770-532-4444 
mthomas@gainesvilleeye.com 
770-532-4444 
 
Further, depending upon the nature of the adverse event (serious or nonserious) 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 device 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 device has not been 
demonstrated, but there is a reasonable possibility that the adverse 
event or quality complaint was caused by the medical device. 
 
 

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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. 
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. 
13.4. 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.  
13.5. Safety Analyses 
The type, severity, duration and frequency of reported ocular adverse events will be 
tabulated.  Adverse events will also be summarized for events that were considered 
treatment-related.   
14. 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. 
 

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The study will be registered with clinicaltrials.gov. 
 
14.1 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.  
 
 

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15.  STANDARD EVALUATION PROCEDURES  
Table 15.1. Proposed Visits and Study Assessments 
                  (visits are by patient, with both eyes tested) 
 
 
Activity 
Pre-
operative 
Operative 
Postoper
ative 
 
 
 
 
 
Visit 1 
Visit 2a,2b 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
 
 
POD  
17-28 
POD  
24-42 
POD  
31-56 
POD 
38-63 
POD 
45-70 
POD 90 
Informed Consent 
L,C 
 
 
 
 
 
 
 
Demographics 
L,C 
 
 
 
 
 
 
 
General Information:   
Medical History 
L,C 
 
 
 
 
 
 
 
Surgery 
 
L,C 
 
 
 
 
 
 
Manifest refraction 
L,C 
 
L,C 
L 
L 
L 
L 
L,C 
Monocular uncorrected 
distance VA 
L,C 
 
L,C 
L 
L 
L 
L 
L,C 
Monocular corrected distance 
VA 
L,C 
 
L,C 
L 
L 
L 
L 
L,C 
Binocular uncorrected and 
best-corrected distance VA 
 
 
L,C 
L 
L 
L 
L 
L,C 
Monocular uncorrected and 
best distance-corrected 
intermediate VA (66cm) 
 
 
L,C 
L 
L 
L 
L 
L,C 
Binocular uncorrected and 
best distance-corrected 
intermediate VA (66cm) 
 
 
L,C 
L 
L 
L 
L 
L,C 
Monocular uncorrected and 
best distance-corrected near 
VA (40cm) 
 
 
L,C 
L 
L 
L 
L 
L,C 
Binocular uncorrected and 
best distance-corrected near 
VA (40cm) 
 
 
L,C 
L 
L 
L 
L 
L,C 
Monocular Distance 
Corrected Defocus Curve 
 
 
 
 
 
 
 
L,C 
Binocular Defocus Curve 
(Dominant eye: plano 
corrected, non-dominant: -
1.00D) 
 
 
 
 
 
 
 
L,C 
PRSIQ questionnaire 
 
 
L,C 
 
 
 
 
L,C 
Total ocular, corneal and 
internal HOA and SA with 
iTRACE 
(Both eyes in LAL group and 
dominant eye for Clareon 
group) 
 
 
L 
L 
L 
L 
L 
L,C 
Number of days and post-op 
office visits from cataract 
surgery to routine "release of 
care visit” (i.e. final lock-in for 
LAL group, 17-28 days after 
2nd eye surgery for Clareon 
group) 
 
 
 
 
 
 
 
L,C 
Monitor for Adverse Events 
and Device Deficiencies 
 
L,C 
L,C 
L,C 
L,C 
L,C 
L,C 
L,C 
Complete Exit Form1 
 
 
 
 
 
 
 
L,C 
C = Clareon Group; L = LAL group 
1 Complete Exit Form upon termination of subject participation, or at Visit 8, whichever occurs first. 

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16. DATA CONFIDENTIALITY 
No protected health information (PHI), including the patient’s name and date of birth, 
will be collected; to ensure this, no PHI information is permitted to be entered on any of 
the Case Report Forms (CRFs). Subjects will only be identified by subject IDs and 
identities will be removed at the initial visit so that there is no further need to protect or 
destroy the information. Collected information will only be used for purposes of this 
study and no information will be sold to third parties. The non-PHI information collected 
may be used for future research, though there is currently no plan to do so.  
17. FINANCIAL AND INSURANCE INFORMATION/STUDY RELATED 
INJURIES 
Every effort to prevent study-related injury will be taken by the Study Doctor and staff. 
In the event a patient is injured as a direct result of the study while following the Study 
Doctor’s instructions and the study requirements, the patient will be instructed to contact 
his or her doctor immediately. The Study Doctor is to treat the injured subject as needed 
for those injuries caused directly by this research study. In the event of injury or illness 
caused by or occurring during a subject’s participation in this research study, all charges 
for medical care provided to the subject will be billed to his or her insurance company. 
The Study Doctor or Sponsor does not offer to cover the medical care costs for injuries or 
illnesses that are not caused directly by the research study. The Sponsor does not offer to 
provide any other compensation, unless specifically agreed to elsewhere in this 
document. This information will be provided to each study subject before the start of the 
study in the consent form. 
18. STUDY ENDPOINT CRITERIA 
18.1. Patient Completion of Study  
If a study patient has completed the final visit (Visit 8) of the study, he/she is considered 
to have completed the study.  
 18.2. Patient Discontinuation  
Each study patient may voluntarily discontinue the study at any time they choose.  Study 
patients who cannot complete the study for administrative reasons (e.g., non-compliance, 
failure to meet visit schedule, etc.) will be discontinued from the study.  Study patients 
discontinued during the enrollment phase (prior to surgery) of the study will be replaced.  
 18.3. Patient Termination  
A study patient will be terminated if the study patient develops any severe adverse event 
that may be related to the study.  A study patient will receive appropriate treatment at the 
discretion of the investigator.  Notification of termination will be clearly documented.  
These study patients are considered to have completed the study and will not be replaced.   

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18.4. Study Termination 
The investigator with appropriate notification may terminate the study.  If, after clinical 
observations, the investigator feels that it may be unwise to continue the study, he may 
stop the study.   
18.5. Study Completion  
The study will be complete when all enrolled patients have completed Visit 8 or have 
been terminated from the study.   
19. SUMMARY OF RISKS AND BENEFITS 
19.1. Summary of risks 
The risks with this study are similar to those for any patient receiving cataract surgery 
and IOL implantation.1,2 There is no increased risk associated with the proposed study. 
19.2. Summary of benefits 
Studies of Clareon and LAL IOLs have demonstrated that patients are likely to have 
relatively good visual outcomes.1,2  
 
Subjects may be compensated up to $200 for completing the study.  
 
REFERENCES 
1. 
Blehm C, Hall B. Evaluation of visual outcomes and 3-month refractive stability 
of a new hydrophobic acrylic intraocular lens. Clinical Ophthalmology. 
2023;17:1859-1864. 
2. 
Moshirfar M, Henrie MK, Payne CJ, Hansen AM, Ronquillo YC, Hoopes PC. 
Comparing visual outcomes of light adjustable intraocular lenses in patients with 
and without prior history of corneal refractive surgery. J Refract Surg. 
2023;39(5):311-318.