Long Term Safety Follow-up for Subjects Previously Implanted With the ACRYSOF® CACHET® Phakic Lens in Clinical Studies C-02-23, C-02-40, C-03-21 and C-05-57
Phase: NA
Conditions: Myopia
Sponsor: Alcon Research

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Document: TDOC-0010249 
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Short Title 
 
Long Term Safety Protocol for AcrySof® CACHET® Phakic Lens 
Long Title 
Long Term Safety Follow-up for Subjects Previously Implanted with the AcrySof® 
CACHET® Phakic Lens in Clinical Studies C-02-23, C-02-40, C-03-21 and C-05-57 
 
1. TITLE PAGE 
 
Protocol Number: 
C-09-043/ NCT01497067 
 
Medical Specialty: 
Surgical IOL 
Project Name /Number: 
Angle-Supported Phakic Refractive IOL / 25-5223 
Sponsor Name & Address: 
Alcon Research, Ltd. 
6201 South Freeway 
Fort Worth, Texas 76134-2099 
 
Test Article(s) / Product(s): 
AcrySof® CACHET® Phakic Lens 
Models L12500, L13000, L13500 and L14000 
 
 
Clinical Investigator: 
 
Signature 
Date 
Name & Inv. # 
Address 
Telephone 
As listed on the Statement 
of Investigator 
 
 
In signing you agree that you have read, understand and will adhere to this protocol. 
See last page for electronic approvals. 
 
 
 
 
 
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2. SUMMARY 
 
 
Study Phase: 
Not applicable 
 
Financial Disclosure 
Information for U.S. FDA 
Submission to be Obtained? 
Yes 
No 
 
 
Test Article(s) / Product(s): 
AcrySof® CACHET® Phakic Lens (L-series) 
Study Dosage / Usage: 
Intraocular lenses are implantable medical devices and 
are intended for long term use over the lifetime of the 
subject. The phakic intraocular lens may be removed as 
needed (e.g. cataract extraction). 
Active Ingredients: 
Not applicable 
Route of Administration: 
Not applicable 
 
Objective(s): 
The primary objective is to estimate the annualized 
endothelial cell loss rate (for up to 10 years following 
date of implantation) of subjects previously implanted 
with the ACRYSOF CACHET Phakic Lens (L-series) 
from clinical studies C-02-23, C-02-40, C-03-21 and C- 
05-57. 
The secondary objective is to collect additional safety 
data that may identify risk factors for eyes with 
significant endothelial cell loss. 
Study Population: 
Subjects previously implanted with the ACRYSOF 
CACHET Phakic Lens (L-series) during clinical studies 
C-02-23, C-02-40, C-03-21 and C-05-57 (includes 
subjects who have had the lens explanted for any 
  
reason). 
 
Structure: 
Parallel Group 
Duration of Treatment: 
Duration of Assessment: 
 
Crossover 
Number of Treatments: 
Number of Sequences: 
Number of Periods: 
Duration of Periods: 
Washout Between 
Yes 
No 
Periods: 
 
Other 
No control, open label study 
Duration of Treatment: Subjects to be followed 
for 5 to 7 years (10 years from the time of 
implantation). 
X 
X 

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Status: Effective 
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Multi-center: 
X   Yes 
Number of Centers: Up to 35 
No 
 
Masking: 
None 
Observer-Masked 
Patient-Masked 
Double-Masked 
 
 
 
 
Randomization: 
Yes Group Assignment Ratio: 
No 
 
 
Concurrent 
Control: 
None 
No Treatment 
Placebo 
Active 
Specify: 
Other 
Specify: 
 
 
 
Estimated Total Sample Size: Required: N/A 
Planned: Up to 1321 eyes 
 
Statistical Rationale Provided: 
Yes 
See Section 11 
No 
 
Variable(s): 
Primary Efficacy 
• None 
Secondary Efficacy 
• None 
 
Primary Safety 
• Central endothelial cell density 
• Adverse events 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 

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X 
Descriptive statistics will be provided for central 
endothelial cell densities, 
Status: Effective 
C09043 
Both volunteered and elicited 
Adverse Events: 
Other: 
 
 
Analyses: The primary objective is to estimate the annualized endothelial cell loss rate (for 
up to 10 years following date of implantation) of subjects previously implanted with the 
ACRYSOF CACHET Phakic Lens (L-series) from clinical studies C-02-23, C-02-40, C-03- 
21 and C-05-57. 
 
Combining data from this study with the data from the subjects’ previous studies, the rate of 
endothelial cell density loss between consecutive visits will be calculated via a paired analysis 
and descriptive statistics on those rates will be presented. 
 
decrease for each eye from baseline (6 month visit in previous study) to each visit will be 
calculated via a paired analysis and descriptive statistics for the actual and annualized loss 
rates will be presented. 
 
 
The secondary objective is to collect additional safety data that may identify risk factors for 
eyes with significant endothelial cell loss. 
 
Also, the percentage endothelial cell density 

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3. TABLE OF CONTENTS 
 
 
Page 
 
1. 
TITLE PAGE............................................................................... 
1 
1.1. 
Amendments ....................................................................... 
2 
2. 
SUMMARY.................................................................................. 
9 
3. 
TABLE OF CONTENTS ............................................................ 
13 
Table of Tables............................................................................. 
17 
4. 
INTRODUCTION ....................................................................... 
18 
5. 
OBJECTIVE(S) ........................................................................... 
19 
6. 
TEST ARTICLE(S)..................................................................... 
20 
6.1. 
Identification ....................................................................... 
20 
6.2. 
Usage................................................................................... 
21 
6.3. 
Test Article Accountability Procedures .............................. 
21 
7. 
SUBJECTS................................................................................... 
22 
7.1. 
Subject Population .............................................................. 
22 
7.2. 
Inclusion Criteria ................................................................ 
22 
7.3. 
Exclusion Criteria ............................................................... 
22 
8. 
STUDY DESIGN ......................................................................... 
23 
8.1. 
Study Design ....................................................................... 
23 
8.1.1. 
Implant Removals.................................................. 
23 
8.2. 
Methods Used to Minimize Bias......................................... 
23 
8.3. 
Clinical Study Termination................................................. 
24 
8.4. 
Regulatory Documentation and Records Retention............ 
24 
8.5. 
Data Management ............................................................... 
24 
8.6. 
Data Review and Handling ................................................. 
24 
8.7. 
Data Publication.................................................................. 
25 

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TABLE OF CONTENTS - Continued 
Page 
9. 
STUDY PROCEDURE ............................................................... 
26 
9.1. 
Study Visits and Examination............................................. 
26 
9.2. 
Entrance Visit...................................................................... 
27 
9.2.1. 
Informed Consent .................................................. 
27 
9.2.2. 
Inclusion Criteria ................................................... 
28 
9.2.3. 
Enrollment Information ......................................... 
28 
9.2.4. 
Medical History ..................................................... 
28 
 
28 
29 
29 
29 
30 
30 
30 
30 
9.3.7. 
Endothelial Cell Density Analysis......................... 
32 
35 
35 
35 
 
35 
9.4. 
Unscheduled Visits ............................................................. 
36 
9.5. 
Missed Visit – “Subject Unavailable” ................................ 
36 
9.6. 
Discontinued Subjects......................................................... 
37 
9.7. 
Subject Lost to Follow-Up.................................................. 
37 
9.8. 
Patient Pregnancy................................................................ 
37 
 
10.   ANALYSIS PLAN ....................................................................... 
38 
10.1.   Subject Evaluability ............................................................ 
38 
10.2.   Analysis Data Sets .............................................................. 
38 
10.2.1.  Safety..................................................................... 
38 
10.3.   Demographic and Baseline Characteristics ........................ 
38 

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TABLE OF CONTENTS - Continued 
Page 
 
 
 
10.4.   Safety Analysis ................................................................... 
38 
10.4.1.   Primary Safety ....................................................... 
39 
 
10.4.1.1. Central Endothelial Cell Density .......... 
39 
10.4.1.2. Adverse Events ..................................... 
40 
40 
40 
41 
41 
41 
42 
42 
42 
42 
43 
43 
43 
10.6.   Handling of Missing Data................................................... 
43 
10.7.  Multiplicity ......................................................................... 
43 
43 
11.   SAMPLE SIZE JUSTIFICATION ............................................ 
44 
12. 
ADVERSE EVENTS........... 
45 
12.1.  General Information............................................................ 
45 
12.2.   Procedures for Recording and Reporting............................ 
49 
12.3.   Unmasking of Study Information ....................................... 
51 
12.4.   Follow-Up of Safety Information ....................................... 
51 
13.   REGULATORY AND ETHICAL COMPLIANCE................. 
52 

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TABLE OF CONTENTS - Continued 
Page 
 
 
14.  RESPONSIBILITIES.................................................................. 
52 
14.1.  Investigator Responsibilities............................................... 
52 
14.2.   Sponsor and Monitor Responsibilities ................................ 
52 
15.  CONFIDENTIALITY................................................................. 
53 
16.  REFERENCES ............................................................................ 
54 
17.  STUDY PLAN.............................................................................. 
55 
 
57 
58 
60 

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Table of Tables  
 
Page 
 
Table 12.2.-1:  Contact Information for C-09-043 .............................. 
50 
Table 17.-1:  Study Plan ...................................................................... 
55 

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4. INTRODUCTION 
Angle-supported Phakic intraocular lenses (IOLs) have been shown to be effective in the 
correction of myopia and have several benefits over refractive surgery, including reversibility. 
These IOLs, however, have been associated with complications including possible loss of 
corneal endothelial cells, pupil ovalization, pigment dispersion, inflammation, synechiae, 
cataractogenesis, and pupillary block (Kohnen 2010). Of particular concern is possible 
endothelial cell loss (ECL) which may lead to corneal decompensation. Several factors may 
lead to ECL, one is possible compression forces against anterior chamber structures. In this 
study, endothelial cell density 
will be monitored to assess possible causes of ECL. 
 
 
The ACRYSOF CACHET Phakic IOL is an angle-supported, single-piece, foldable, soft 
acrylic lens with a chemically bonded UV chromophore and a 6.0 mm meniscus optic. This 
lens is designed for placement in the anterior chamber to correct moderate to high myopia and 
provide subjects with a form of vision correction, comfort, and convenience not attainable 
with spectacles or contact lenses. Because the ACRYSOF CACHET Phakic Lens is foldable, 
it can be inserted through a small incision, thus reducing the likelihood of induced 
astigmatism. The mechanical properties of the ACRYSOF material, together with the design 
of the ACRYSOF CACHET Phakic Lens, should result in lower forces against the anterior 
chamber angle. 
 
Phased clinical studies have been completed, or are ongoing, to assess the safety and 
effectiveness of the ACRYSOF CACHET Phakic IOL. Models SA3M25, SA3M13, and 
SA3M35 (the SA-series) were studied as part of European (EU) clinical investigations 
conducted under Protocol C-99-38 (EU Phase 1) and Protocol C-01-22 (EU Phase 2). Models 
RA6M13 and RA6M35 (the RA-series) were studied as part of the U.S. clinical investigation 
conducted under Protocol C-02-23 (U.S. Phase 1). Models L12500, L13000, L13500, and 
L14000 (the L-series) are being studied (two studies are complete) in four protocols: as part of 
an EU clinical investigation conducted under Protocol C-02-40 (EU Phase 3); a completed 
U.S. clinical investigation conducted under Protocol C-02-23 (U.S. Phase 1 (second eyes 
only) and Phase 2); a completed U.S. clinical investigation conducted under Protocol C-05-57 
(U.S. Phase 3); and also as part of a Canadian clinical investigation conducted under Protocol 

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C-03-21 (Canada Phase 3). Interim data from these ongoing clinical trials were reported in 
Kohnen 2009 and Knorz 2011. 
 
Based on the results available to date, the overall risks for subjects implanted with the 
ACRYSOF CACHET Phakic IOL are representative of known risks associated with 
intraocular surgery and the implantation of a phakic IOL. Continued monitoring of 
postoperative corneal health, including endothelial cell density and cell morphology, is 
recommended to ensure safety of the subject. Endothelial cell loss will be followed in this 
study to understand the long-term safety of the ACRYSOF CACHET Phakic IOL (L-series). 
Only L-series IOLs will be followed in this study since this is the model that will be 
submitted for market approval. The ACRYSOF CACHET Phakic IOL is marketed outside 
the United States. 
 
A summary of clinically significant findings from non-clinical and clinical studies and a 
summary of known and potential risks and benefits to human subjects can be found in the 
Clinical Investigator’s Brochure (CIB-0021; TDOC-0006479) for the ACRYSOF CACHET 
Phakic IOL family including the following models:  Models SA3M25, SA3M13, and 
SA3M35 (the “SA” series, all with a 5.5 mm diameter optic size), Models L12500, RA6M13 / 
L13000, RA6M35 / L13500, and RA6M14 / L14000 (the “RA” series and “L” series all have 
a 6.0 mm diameter optic size). 
 
 
5. OBJECTIVE(S) 
The primary objective is to estimate the annualized endothelial cell loss (ECL) rate (for up to 
10 years following date of implantation) of subjects previously implanted with the ACRYSOF 
CACHET Phakic Lens (L-series) within clinical studies C-02-23, C-02-40, C-03-21 and C- 
05-57. 
 
The secondary objective is to collect additional safety data that may identify risk factors for 
eyes with significant ECL. 

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Ø6.0 
 
6. TEST ARTICLE(S) 
 
 
6.1. Identification 
Lenses will not be supplied during this clinical trial, as subjects invited to enroll will have 
been previously implanted with the ACRYSOF CACHET Phakic Lens (L-series) from 
clinical studies C-02-23, C-02-40, C-03-21 and C-05-57. 
 
The ACRYSOF CACHET Phakic Lens is an angle-supported, anterior chamber, single piece 
lens composed of a cross-linked soft acrylic polymeric material with a chemically bonded 
UV-absorber. This is the same acrylic material that is currently used in the optic of the 
globally marketed ACRYSOF multi- and single-piece IOL Models MA30BA, MA60BM, 
SA30AL, and SA60AT. 
 
The ACRYSOF CACHET Phakic Lens models have a 6.0 mm diameter meniscus optic and 
are intended for implantation in the anterior chamber angle. The overall lengths of these 
models vary from 12.5 mm to 14.0 mm as follows: Models L12500 (12.5 mm), L13000 (13.0 
mm), L13500 (13.5 mm) and L14000 (14.0 mm). The dioptric range of these IOLs is -6 to - 
16.5D. 
 
 
 
 
 
 
OVERALL 
LENGTH 
(OAL) 
 
6 mm 
OAL (mm) Model 
12.5 
L12500 
13.0 
L13000 
13.5 
L13500 
14.0 
L14000 

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6.2. Usage 
The ACRYSOF CACHET Phakic Lens is a permanent implantable medical device, thus the 
expected duration of individual subject use, and exposure, is expected to be for the remainder 
of the subject’s life, or until cataract extraction is needed. 
 
 
6.3. Test Article Accountability Procedures 
Damaged test articles or explanted lenses must be packaged in a biohazard bag and returned 
to the sponsor at the following address: 
 
Attn: 
Mail Code: 
Alcon Research, Ltd. 
6201 South Freeway, 
Fort Worth, TX 76134 
 
 
In cases of explanted lenses, all information related to the adverse device effect or serious 
adverse event should be entered into the EDC system on the Adverse Device Effect and 
Serious Adverse Event Form within 24 hours of the investigator’s or site’s awareness of the 
event. Please include a printed copy of the completed Adverse Device Effect and Serious 
Adverse Event Form with product returns. 
 
Refer to Section 12 for additional information on reporting any 
, adverse 
device effects, or serious adverse events. 

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7. SUBJECTS 
 
7.1. Subject Population 
Subjects previously implanted (unilaterally or bilaterally) with the ACRYSOF CACHET 
Phakic Lens (L-Series) in clinical studies C-02-23, C-02-40, C-03-21 and C-05-57 (includes 
subjects who have had the lens explanted for any reason). Up to 778 subjects will be 
enrolled; up to 65 subjects per site. No vulnerable population is planned. 
 
 
7.2. Inclusion Criteria 
1. 
Subjects previously implanted (including subjects who have had the lens explanted for 
any reason) with an ACRYSOF CACHET Phakic Lens (L-Series) from clinical studies 
C-02-23, C-02-40, C-03-21 and C-05-57 and are eligible for continued follow-up (ie, 
exited from their previous study). 
2. 
Subjects are willing and able to complete the yearly postoperative study visits. 
3. 
Subjects are able to understand and sign a statement of informed consent. 
 
 
7.3. Exclusion Criteria 
None 

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8. STUDY DESIGN 
 
8.1. Study Design 
Subjects enrolled in this study will attend postoperative visits for up to 10 years following the 
date of implantation and will be able to enroll at any time for the duration of this trial. These 
subjects will be followed postoperatively to Year 10/10A (3619 – 3740 days) at appropriate 
intervals as defined in Section 9.1. 
 
 
 
8.1.1. IMPLANT REMOVALS 
During this clinical investigation, the implant may be removed at any time at the request of 
the study subject and/or if the investigator believes it appropriate (eg, cataract surgery). An 
implant removal is considered a Secondary Surgical Intervention and requires the completion 
of a Serious Adverse Event Form (see Section 12). Test article will not be provided for IOL 
replacement. Subjects with implant removals will not be exited from the study. 
 
 
8.2. Methods Used to Minimize Bias 
Randomization and masking are not used in this study. However, all investigators and study 
coordinators will receive common training (including specular image collection and angle 
measurements) to ensure consistent application of the methods specified in the protocol. 
Also, the same inclusion criteria are to be applied by all investigators and all patients meeting 
inclusion criteria will be invited to participate in the study. Furthermore, explanted subjects 
will not be discontinued. Bias will also be minimized by using a central reading center for 
corneal endothelial cell analysis. In addition, study duration will be sufficient to examine the 
effect of the lens on endothelial cells (ie, density 
). 

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8.3. Clinical Study Termination 
An investigational site can be suspended or terminated by the Sponsor if monitoring or 
auditing identifies serious or repeated deviations. While possible, it is not anticipated that the 
entire study will be terminated. If the study or an investigational site is terminated, the 
investigator and any regulatory authorities will be informed with 5 days of the decision. 
Investigators would be given instructions for the procedures to be followed to assure that 
adequate consideration is given to the protection of the patient’s interests. The investigator 
will be responsible for informing IEC/IRB’s of the early termination of the trial or of the 
investigational site. 
 
 
8.4. Regulatory Documentation and Records Retention 
Essential documents must be retained by the Investigator for as long as needed to comply 
with national and international regulations (generally 2 years after discontinuing clinical 
development or after the latest marketing approval). The Sponsor will notify the 
Investigator(s)/institution(s) when the study-related records are no longer required. 
 
 
8.5. 
Data Management 
A Clinical Data Management System (CDMS) will be used to collect and validate clinical 
data. The CDMS will conform to the Sponsor’s requirements for system setup and data 
security. Data validation will be performed by electronically generated checks and manual 
reviews. Final data and related documentation will be retained according to the Sponsor’s 
retention schedule. 
 
 
8.6. 
Data Review and Handling 
Clinical data captured at the sites will be entered into electronic case report forms (eCRFs) 
within the CDMS. SAS datasets  (SAS Institute Inc. Cary, NC , USA) for the clinical data 
will be downloaded from the electronic data capture (EDC) database after database lock, or as 
needed throughout the clinical trial. All SAS datasets will be housed in a secured network 
area storage and will be accessible to the Sponsor using read only roles. The datasets will 
reflect the current protocol. The datasets will reflect the current state of the database, all 

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previous actions and values of the data will be captured in the audit trail within the EDC 
database. 
 
Any change or correction to data reported on a CRF will be updated and/or explained within 
the CDMS. The original entry and all actions applied to the CRF after initial entry will be 
maintained in the audit trail (ie, an audit trail will be maintained that documents the action, 
user and date of change or explanation). 
 
 
8.7. 
Data Publication 
Results will be published through clinicaltrials.gov. 

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9. STUDY PROCEDURE 
 
9.1. Study Visits and Examination 
An Entrance Visit will be completed upon a subject’s enrollment. Subjects may enroll in the 
study at any time, thus the Entrance Visit may coincide with any visit (Year 4/4A to Year 
10/10A ). 
 
1 Only eyes previously implanted with an L-series lens are eligible for enrollment. 
2”A” designates forms that are completed for a Subject’s 2nd implanted eye. 
Note: In some cases, more than six months may have passed since a subject completed the previous 
study. These subjects will be examined at the next appropriate time-point following entrance to the 
study. 
C-09-043 Study Visits 
Previous Eligible Studies1 
Year 10/10A 
3619 – 3740 days postop. 
Year 9.5/9.5A 
3436 – 3557 days postop. 
Year 9/9A 
3254 – 3375 days postop. 
Year 8/8A 
2889 – 3010 days postop. 
Year 8.5/8.5A 
3071 – 3192 days postop. 
Year 7/7A 
2524 – 2645 days postop. 
Year 7.5/7.5A 
2706 – 2827 days postop. 
C-02-23 (following 
the 5 yr. visit for 
the 1st implanted 
eye) 
C-02-40 (5 yr. study) 
C-03-21 (5 yr. study) 
Year 6/6A 
2159 – 2280 days postop. 
Year 6.5/6.5A 
2341 – 2462 days postop. 
Year 5.5/5.5A 
1976 – 2097 days postop. 
Year 5/5A 
1794 – 1915 days postop. 
Year 4/4A 
1429 – 1550 days postop. 
C-02-23 (following 
the 3 yr. visit for 
the 2nd implanted 
eye) 
C-05-57 (3 yr. study) 

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Postoperative visits for the first and second implants may be performed simultaneously if both 
visits fall within the proper timeframes specified for each eye. 
 
Subjects examined subsequent to Day 3740 and prior to study exit (eg, a planned visit 
occurring after the last study plan visit) will be included in the Year 10/10A analysis if: 
 
 
a) no Year 10 or 10A Form was received previously, or 
b) the original Year 10 or 10A exam was early, or 
c) the subject was previously unavailable for the visit or previously discontinued. 
 
Each required examination must be recorded on the corresponding electronic Case Report 
Forms (eCRFs) in a timely manner. 
 
 
9.2. 
Entrance Visit 
The following information will be recorded on the Entrance Visit eCRF: 
 
 
9.2.1. INFORMED CONSENT 
Prior to undergoing study specific measurements, subjects will be asked to give 
informed consent and sign the Institutional Review Board (IRB) or Institutional Ethics 
Committee (IEC) approved Informed Consent Document (ICD). Only subjects who 
have signed the informed consent and qualified to be in the study by meeting all 
inclusion criteria will be enrolled into the study. 
 
The Investigator, or designee, will explain the clinical trial to each potential subject 
and the subject must indicate voluntary consent by signing and dating the approved 
informed consent form. The subject must be provided an opportunity to ask questions 
of the Investigator, and if required by local regulation, other qualified personnel. The 
Investigator must provide the subject with a copy of the consent form written in a 
language the subject understands. The consent document must meet all applicable 
local laws and will provide subjects with information regarding the purpose, 

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procedures, requirements, and restrictions of the clinical trial, along with any known 
risks and potential benefits associated with the investigational product, the available 
compensation, and the established provisions for maintaining confidentiality of 
personal, protected health information. Subjects will be told about the voluntary 
nature of participation in the clinical trial and will be provided with contact 
information for the appropriate individuals should questions or concerns arise during 
the clinical trial. The subject also will be told that their records may be accessed by 
appropriate authorities and Sponsor-designated personnel. The Investigator must keep 
the original, signed copy of the consent and must provide a duplicate copy to each 
subject. 
 
 
9.2.2. INCLUSION CRITERIA 
Refer to the list of Inclusion criteria in Section 7.2. to ensure that the subject meets all 
qualifications for participation (ie, inclusion criteria). 
 
 
9.2.3. ENROLLMENT INFORMATION 
 
Record the following information from the subject’s previous (C-02-23, C-02-40, C- 
03-21, or C-05-57) study: Protocol number, investigator number, subject number, 
study eye(s), whether or not the lens was replaced, and the Visit in which the subject 
entered the C-09-043 study.  If the fellow eye has been implanted with any Phakic 
IOL (at any time), or if the ACRYSOF CACHET Lens has been replaced with another 
IOL, please record lens information (“other IOL”). 
 
 
9.2.4. MEDICAL HISTORY 
Record all relevant ocular and relevant non-ocular medical history. 
 
 

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9.3.7. ENDOTHELIAL CELL DENSITY ANALYSIS 
Endothelial cell density 
will be measured using the same methods as 
in the previous studies (C-02-23, C-02-40, C-03-21, C-05-57). The Konan Noncon- 
Robo specular microscope will be used to photograph corneal endothelial cells. Three 
 
 
Images shall be stored on the computer hard drive at the clinical site. Electronic 
copies of the images will be sent to a central reading center for analysis. For 
consistency, the central reading center ( 
) used for the previous 
studies, will be used for this study; Alcon personnel will not be involved in image 
analysis.  The process for analyzing images at 
 will remain 
unaltered from that done in previous studies. Briefly, images received at 
will be reviewed by an initial reader and assessed for image quality. If 
image quality is acceptable then images will be analyzed. If images are deemed 
unanalyzable, then images will not be analyzed, and the site and Sponsor will be 
notified. (If there is a trend of unanalyzable images for a specific site/delegated study 
images at the center of the cornea 
shall be obtained. 

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personnel, retraining will be provided.) The subject will be asked to return and repeat 
the image capture and new images will be analyzed and used in the dataset. Analyzed 
images will be audited by a quality control reviewer 
 
Data reported by the central reading center will include endothelial cell density, 
 
The site will receive a copy of the analysis to 
enter results in eCRFs. 
 
 
The critical ECD threshold needed to sustain corneal endothelial cell function varies 
among individuals. Thus, it is critical to have regular examinations of the cornea every 
6 months. 
 
Criteria that may warrant more frequent examinations include: 
• <1500 cells/mm2 (central 
) 
• >10% ECL in one year 
• >30% ECL from preoperative baseline 
 
 
When the central ECD approaches approximately 1500 cells/mm2, the investigator should 
consider the potential need to undergo IOL explantation to reduce the risk of corneal 
decompensation and subsequent surgical interventions (such as corneal transplantation or 
DSEK). 
 

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9.4. 
Unscheduled Visits 
 
If a subject is examined more than once during any of the scheduled follow-up periods or if 
the subject is examined between scheduled follow-up periods, or if there is an unscheduled 
planned treatment delaying exit, an Unscheduled Visit Form must be completed. 
 
 
If, during the visits for the 2nd eye implanted (Year 4A through 10A Forms), a clinically- 
relevant finding is noted for the 1st eye implanted, an unscheduled visit form must be 
completed to record the data for the 1st eye implanted; the same is true if a clinically-relevant 
finding is noted on the 2nd eye during the visits for the 1st eye. If the second eye examination 
is being conducted at the same time as a scheduled first eye examination (with both 
examinations occurring during the correct time frame) the findings from each eye should be 
recorded on the applicable visit form and not on an unscheduled visit form. 
 
 
9.5. 
Missed Visit – “Subject Unavailable” 
 
If a subject unavoidably misses a scheduled exam, all reasonable efforts must be made to have 
the subject rescheduled within the same exam follow-up period. The investigator must show 
diligence in trying to schedule the subject for all of their postoperative exams. All attempts to 
contact the subject must be documented in the source documentation and the subject’s 
medical records. If an exam cannot be rescheduled, the corresponding visit pages will be 
marked “missed visit, subject unavailable”. Please do not classify the subject as "unavailable" 
until rescheduling has been attempted and the time frame for the postoperative exam has 
expired. 
 
 
If a subject is unable to return for the final study visit (Year 10 or 10A), complete the Exit 
Form with the appropriate reason for discontinuation indicated. 

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9.6. Discontinued Subjects 
 
Discontinued subjects will not be replaced. If a subject is discontinued from the study due to 
their death, the Exit Form and a Serious Adverse Event/Adverse Device Effect Form must be 
completed. 
 
 
Subjects who require an IOL explant will not be discontinued and all reasonable efforts must 
be made to follow them up through their final study visit (Year 10/10A). 
 
 
9.7. 
Subject Lost to Follow-Up 
 
A subject is considered lost to follow-up if: 
 
a) a postoperative Study Visit is overdue, all efforts to contact the subject for an examination 
have failed, the subject’s last visit window has closed, or 
b) the subject is unable to make future office visits, or 
c) the subject has moved and is no longer able to be examined. 
 
If a subject moves before completing all of the required visits, reasonable efforts must be 
made for the subject to return to the implanting investigator or to the closest investigational 
site for follow-up. Reimbursement for reasonable travel costs may be available from the 
Sponsor and will be addressed on a case-by-case basis. 
 
 
9.8. Patient Pregnancy 
Subjects who become pregnant during the study will not be discontinued. 

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10. ANALYSIS PLAN 
 
10.1. Subject Evaluability 
All subjects enrolled in the study will be considered evaluable for the safety analysis. The final 
evaluability (exclusion of post-explantation endothelial cell density data) will be determined 
prior to database lock. 
 
10.2. Analysis Data Sets 
 
10.2.1. SAFETY 
All data collected in the study will be considered evaluable for the safety analysis with one 
exception. For subjects who have their ACRYSOF CACHET L-series Phakic Lens explanted 
and not replaced with another ACRYSOF CACHET L-series Phakic Lens, the post-explantation 
endothelial cell density data will be excluded from the statistical analyses. The post-explantation 
data will be used in subject narratives and graphs. 
 
 
10.3. Demographic and Baseline Characteristics 
Demographic and baseline information from the subjects’ previous study will be summarized 
using frequency distributions for categorical parameters and descriptive statistics (number, 
median, minimum, maximum, mean and standard deviation) for continuous parameters. 
 
 
10.4. Safety Analysis 
The safety parameters include: 
• Central Endothelial Cell Density 
• Adverse Events 

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The primary objective is to estimate the annualized endothelial cell density loss rate (for up to 10 
years following date of implantation) of subjects previously implanted with the ACRYSOF 
CACHET Phakic Lens (L-series) from clinical studies C-02-23, C-02-40, C-03-21 and C-05-57. 
 
The secondary objective is to collect additional safety data that may identify risk factors for eyes 
with significant endothelial cell density loss. 
 
 
10.4.1. PRIMARY SAFETY 
 
10.4.1.1. CENTRAL ENDOTHELIAL CELL DENSITY 
Descriptive statistics for central endothelial cell density, for each scheduled visit (including data 
from previous studies), will be provided. Descriptive statistics for central endothelial cell 
density chronic change (actual and percent) from baseline (6 month visit in previous study) to 
each scheduled visit will be provided. Descriptive statistics for central endothelial cell density 
change (actual and percent) between consecutive scheduled visits will be provided. All tables 
will be generated separately for first implanted eye, second implanted eye, and for both 
implanted eyes combined. Descriptive statistics include mean, median, standard deviation, 
sample size, minimum, maximum and confidence limits. 
 
The mean rate of endothelial cell density decrease will be calculated via a paired analysis in 
order to calculate the mean of the differences between each reporting period. 
 

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10.4.1.2. ADVERSE EVENTS 
Descriptive statistics (number and percent of eyes) will be presented for each MedDRA 
Preferred Term category of ocular adverse events and serious ocular adverse events reported, 
separately for first implanted eye, second implanted eye, and for both implanted eyes combined. 
Descriptive statistics (number and percent of subjects) will be presented for each MedDRA 
Preferred Term category of non-ocular adverse events and serious non-ocular adverse events 
reported. A listing of all adverse events and serious adverse events reported during the study will 
also be provided. 

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10.6. Handling of Missing Data 
All evaluable data will be used in the analyses; however, no imputation will be carried out for 
missing data. 
 
 
10.7. Multiplicity 
No formal hypothesis testing is planned for any parameters and therefore no multiplicity 
adjustments are needed. 
 
 

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11. SAMPLE SIZE JUSTIFICATION 
The sample size will reflect the number of sites and subjects agreeing to participate. 
 
 
All available and willing subjects meeting inclusion criteria will be included in the study (up 
to 778 subjects; up to 1321 eyes). 

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12. 
ADVERSE EVENTS 
 
12.1. General Information 
 
 
Definitions 
 
Adverse Event (AE) – any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device. Note: For subjects, this 
definition includes events related to the investigational medical device or the procedures 
involved. For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
 
See Figure 12.1.-1 for categorization of adverse events. 
 
 
Adverse Device Effect (ADE) – adverse event related to the use of an investigational medical 
device. Note: This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation; any malfunction; 
and use error or intentional misuse of the investigational medical device. 
 
Nonserious Adverse Event - adverse event that does not meet the criteria for a serious 
adverse event. 
 
Serious Adverse Event (SAE) - adverse event that led to any of the following: 
• Death. 
• A serious deterioration in health that either resulted in: 

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a) a life-threatening illness or injury. 
Note: Life-threatening means that the individual was at immediate risk of death from 
the event as it occurred, ie, it does not include an event which hypothetically might 
have caused death had it occurred in a more severe form. 
b) any potentially sight-threatening event or permanent impairment to a body structure or 
a body function. 
c) in-patient hospitalization or prolonged hospitalization. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by 
the clinical investigation plan, without serious deterioration in health, is not 
considered a serious adverse event. 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 adverse events. 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. 
d) a medical or surgical intervention to prevent a) or b), or any ocular secondary 
intervention. 
e) any indirect harm as a consequence of incorrect diagnostic test results when used 
within manufacturer's instructions for use. 
• Fetal distress, fetal death, or a congenital abnormality or birth defect. 
 
See Figure 12.1.-2 for categorization of SAEs. 
 
 
Serious Adverse Device Effect (SADE) – adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event. 
 
Anticipated Serious Adverse Device Effect (ASADE) – serious adverse device effect which 
by its nature, incidence, severity or outcome has been identified in the risk analysis. 
 
Unanticipated Serious Adverse Device Effect (USADE) – serious adverse device effect 
which by its nature, incidence, severity or outcome has not been identified in the risk analysis. 

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Device/ 
procedure - 
related? 
 
 
Figure 12.1.-1: Categorization of All Adverse Events 
 
 
 
 
 
 
 
 
NO 
NO 
 
 
 
 
YES 
YES 
 
 
 
 
 
 
Figure 12.1.-2: Categorization of All Serious Adverse Events 
 
 
 
 
 
 
 
 
NO 
 
 
 
 
 
 
NO 
 
 
 
YES 
 
Anticipated 
SADE 
SAE 
ADE 
ALL AEs 
Meet 
seriousness 
criteria? 
AE 
ALL SAEs 
Device/ 
procedure- 
related? 
YES 
SADE 
Anticipated? 
Unanticipated 
SADE 
SAE 

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Specific Events Relevant to this Protocol 
In addition to reporting all adverse events (serious and non-serious) meeting the above 
definitions, the investigator must report any occurrence of the following serious adverse 
events as reported in the previous investigational protocols: 
 
• Pupil ovalization >1 mm 
• Hypopyon 
• Intraocular infection/endophthalmitis 
• Lens dislocation 
• Macular edema (diagnosed clinically or confirmed by fluorescein angiography and/or 
optical coherence tomography) 
• Pupillary block 
• Hyphema 
• Cataract formation 
• Retinal detachment or retinal detachment repair 
• Synechiae 
• Corneal haze if associated with a loss of 2 lines or more (0.2 logMAR or more) of best 
corrected visual acuity (BCVA) from preoperative baseline 
• Any secondary surgical intervention except retinal detachment repair (e.g., iridectomy 
for pupillary block, IOL repositioning, IOL removal due to inflammation, IOL 
replacement, and procedures that may be reported as “other”) 
• Corneal stromal edema (Grade 3) 
• Iritis (aqueous cells or flare of Grade 3 or higher) 
• Raised IOP requiring treatment 
• Loss of 2 lines or more (0.2 logMAR or more) of best spectacle-corrected visual 
acuity (BCVA) from preoperative baseline 
Any other potentially sight-threatening events are also considered serious and have to be 
reported appropriately by the investigator as delineated in Section 12.2. 

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12.2. Procedures for Recording and Reporting 
All adverse events will be documented on the Adverse Event electronic case report form 
(eCRF) within the Electronic Data Capture (EDC) system and collected on a routine basis at 
monitoring visits. Adverse events must be collected from the time of informed consent. 
 
In addition, the investigator must document all ADEs, SAEs, 
with 
details including the date of occurrence, severity, treatment (if applicable), outcome, and 
assessments of the seriousness and causality. The site must submit all available information to 
the study sponsor immediately as follows: 
 
• ADEs or SAEs are documented on the Adverse Device Effect and Serious Adverse 
Event Form in the EDC system within 24 hours of the investigator’s or site’s 
awareness. 
• 
 
 
 
 
• Additional relevant information after initial reporting is to be updated in the 
EDC system as soon as the data becomes available. 
• Document any changes to the medical history and concomitant medication on the 
appropriate forms in the EDC system. 
• All relevant documentation such as Discharge Summary, Autopsy Report, 
Certificate of Death etc, should be faxed to the study sponsor at 
. 
 
Note: Should the EDC system become non-operational, the site must complete the 
appropriate paper Adverse Device Effect and Serious Adverse Event Form 
The completed form is faxed to the study sponsor at 
within 24 hours of the investigator’s or site’s awareness; however, the reported 
information must be entered into the EDC system once it becomes available. 
 
Study sponsor contact information is provided in Table 12.2.-1. 

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Table 12.2.-1: 
Contact Information for C-09-043 
 
Study Staff 
Business Phone 
Business Fax 
Clinical Trial Manager: 
, PhD 
 
 
Clinical Site Management: 
 
 
Medical Monitor: 
MD, MBA, CPE, 
FAAO 
 
 
 
Further, depending upon the nature of the adverse events 
 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 
that could have 
led to a SADE according to the requirements of regulatory authorities or IRB/IEC. 
 
Intensity and Causality Assessments 
For every adverse event 
, the investigator must assess the causality as 
Related or Not Related to the medical device or test procedure in the study. An assessment of 
causality will also be performed by a study sponsor physician utilizing the same definitions, 
as shown below: 
 
Causality 
Related 
An adverse event 
classified as related may be either 
definitely related or possibly related where a direct cause and effect 
relationship with the medical device or test procedure has not been 
demonstrated, but there is a reasonable possibility that the adverse event 
was caused by the medical device or test procedure. 

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Not Related     An adverse event 
classified as not related may either be 
definitely unrelated or simply unlikely to be related (ie, there are other more 
likely causes for the adverse event 
 
). 
 
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. 
 
 
12.3. Unmasking of Study Information 
Not applicable; this study is open-label. 
 
 
12.4. Follow-Up of Safety Information 
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. The investigator should provide the sponsor with any new safety 
information (which includes new adverse events and changes to previously reported adverse 
events) that may affect the safety evaluation of the device. Any additional data from these 
follow-up procedures performed up to 6 months after subject exit must be documented and 
available upon the study sponsor’s request. 

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13. 
REGULATORY AND ETHICAL COMPLIANCE 
This clinical trial will be conducted in accordance with the principles of the Declaration of 
Helsinki, and in compliance with ISO 14155:2011 clinical investigation of medical devices 
for human subjects, Good Clinical Practice (GCP), Code of Federal Regulations (CFR), 
Standard Operating Procedures (SOPs) of Alcon and Contract Research Organizations 
participating in the conduct of the clinical trial, and all other applicable regulations. 
 
 
14. 
RESPONSIBILITIES 
 
14.1. Investigator Responsibilities 
The Investigator will comply with the commitments outlined in the Statement of Investigator 
(Form FDA 1572 or Alcon Form CS006). The Investigator and all clinical trial staff will 
conduct the clinical trial in compliance with this protocol and with GCP and all applicable 
regulatory requirements. The Investigator will ensure that all personnel involved in the 
conduct of the clinical trial are qualified to perform their assigned duties through relevant 
education, training, and experience. 
 
 
14.2. Sponsor and Monitor Responsibilities 
The Sponsor will designate a monitor to conduct the appropriate site visits at the appropriate 
intervals. The clinical investigation will be monitored, following the Monitoring Plan, to 
ensure that: the rights and well being of the patients are protected; the reported data are 
accurate, complete, and verifiable from the source documents; the equipment used to assess 
variables in the clinical investigation is maintained and calibrated per manufacturer 
instructions and Sponsor requirements; the study is conducted in compliance with the current 
approved protocol (and amendment[s], if applicable), with current Good Clinical Practice 
(GCP), and with applicable regulatory requirements. 
 
All studies will have a site initiation. Monitoring will be conducted periodically while the 
clinical study is ongoing. Monitoring methods may include site visits, telephone, written and 
fax correspondence. The Study Manager and/or the assigned Clinical Site Manager will 
contact each site at appropriate intervals. The Lead Clinical Site Manager will determine the 
frequency of site visits. Close-out visits will take place after the last visit of the last patient. 

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15. CONFIDENTIALITY 
The existence of this clinical study is confidential and should not be discussed with persons 
outside of the study. You shall hold confidential, and not disclose directly or indirectly to any 
third party other than those persons involved in the study who have a need to know, the 
protocol, the data arising out of the study, and any other information related to the study or to 
Alcon’s products or research programs that is provided by Alcon to you (the “Confidential 
Information”). All such persons must be instructed not to further disseminate this information 
to others.  You shall not use the Confidential Information for any purpose other than the 
study. The foregoing obligations of confidence and non-use assumed by you shall not apply 
to: (a) information which at the time of disclosure is in the public domain; (b) information 
which thereafter lawfully becomes part of the public domain other than through disclosure by 
or through you; (c) information which, as evidenced by your written records, was known by 
you prior to Alcon’s disclosure; (d) information which is lawfully disclosed to you by a third 
party not under any obligation of confidence to Alcon; or (e) information which is required to 
be disclosed by law or government regulatory agency, provided reasonable advance notice of 
such disclosure is given to Alcon. 
 
All data and discoveries arising out of the study, patentable or nonpatentable, shall be the sole 
property of Alcon, Inc. Alcon reserves the right of prior review of any publication or 
presentation of information related to the study. Alcon may use these data now and in the 
future for presentation or publication at Alcon’s discretion or for submission to government 
regulatory agencies. 

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16. REFERENCES 
 
Bourne WM, Nelson LR, Hodge DO. Central corneal endothelial cell changes over a ten- 
year period. Invest Ophthalmol Vis Sci 1997; 38(3):779-782. 
Hayashi K, Motoaki Y, Shin-ichi M, Hirata A. Cataract surgery in eyes with low corneal 
endothelial cell density. J Cataract Refract Surg 2011; 37:1419-1425. 
Knorz MC, Lane SS, Holland SP. Angle-supported phakic intraocular lens for correction 
of moderate to high myopia: Three-year interim results in international multicenter 
studies. J Cataract Refract Surg. 2011 Mar;37(3):469-80. 
 
Kohnen T, Knorz MC, Cochener B, Gerl RH, Arné JL, Colin J, Alió JL, Bellucci R, 
Marinho A. AcrySof phakic angle-supported intraocular lens for the correction of 
moderate-to-high myopia: one-year results of a multicenter European study. 
Ophthalmology. 2009 Jul;116(7):1314-21. 
 
Kohnen T, Kook D, Morral M, Güell JL. Phakic intraocular lenses: part 2: 
results and complications. J Cataract Refract Surg. 2010 Dec;36(12):2168-94. Review. 
 
McCarey BE, Edelhauser HF, Lynn MJ. Review of corneal endothelial specular 
microscopy for FDA clinical trials of refractive procedures, surgical devices, and new 
intraocular drugs and solutions. Cornea 2008; 27:1-16. 
Yee RW, Matsuda M, Schultz RO, Edelhauser HF. Changes in the normal corneal 
endothelial cellular pattern as a function of age. Curr Eye Res. 1985 Jun;4(6):671-8. 

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17. STUDY PLAN 
 
 
Table 17.-1: 
Study Plan 
 
Nominal Time ± Visit Window Limits 
Entrance 
Visit a 
Year 4/4Ac 
Year 5/5Ad 
Year 
5.5/5.5A 
Year 6/6A 
Year 
6.5/6.5A 
Year 7/7A 
Year 
7.5/7.5A 
Year 8/8A 
Year 
8.5/8.5A 
Year 9/9A 
Year 
9.5/9.5A 
Year 
10/10A 
Procedure / 
Assessment 
Dayb 1429 – 1550 
Day 1794 – 1915 
Day 1976 – 2097 
Day 2159 – 2280 
Day 2341 – 2462 
Day 2524 – 2645 
Day 2706 – 2827 
Day 2889 – 3010 
Day 3071 – 3192 
Day 3254 – 3375 
Day 3436 – 3557 
Day 3619 – 3740 
Informed Consent 
X 
Inclusion/Exclusion 
X 
Enrollment 
Informatione 
X 
Medical History 
X 
Central 
l 
Endothelial Cell 
Photography-3 
images each 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Adverse Events 
(both volunteered 
and elicited) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a The subject’s initial C-09-043 study examination may be Year 4 or later (i.e., Year 4, 5, 5.5, 6, etc.). Point of 
entry is determined by each subject’s eye surgery date and the next available visit listed here to enable 
continued yearly examination. As in previous studies, subjects with the ACRYSOF CACHET Phakic Lens 
(L-Series) implanted in both eyes will have separate study visits, as needed, for each eye to capture the data 
within the window of the annual implant date anniversary. 
b Study Day is relative to the surgery date for each implanted eye. 
c Data from subject’s 2nd implant surgery will be captured on Forms designated with an “A”. 
d A 4.5 Year visit is not included since all patients are past this time-point. 
e The Enrollment Information panel will collect basic information from the subject’s previous study 
(e.g., protocol number, investigator number, subject number, and the first Form/Visit where data is captured in 
this study for each eye). 

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Approval Page 
Safety Protocol for ACRYSOF 
CACHET Phakic Lens 
 
Date/Time 
(mm/dd/yyyy GMT): 
Signed by: 
Justification: 
 
04/17/2013 01:03:55 
Clinical Medical Monitor 
 
 
04/17/2013 18:40:57 
Biostatistics 
 
 
04/17/2013 21:40:36 
Product Safety 
 
 
04/18/2013 16:15:19 
Clinical Study Manager