A Prospective, Multicenter Study to Evaluate the Safety and Performance of the Exchangeable ClarVista HARMONI Modular Toric Intraocular Lens System for the Treatment of Pre-Existing Corneal Astigmatism and Aphakia Following Cataract Surgery
Phase: NA
Conditions: Aphakia, Corneal Astigmatism, Cataract
Sponsor: ClarVista Medical

Short Title 
ClarVista CP-00004 
Long Title 
A PROSPECTIVE, MULTI-CENTER STUDY TO EVALUATE THE 
SAFETY AND PERFORMANCE OF THE 
EXCHANGEABLE CLARVISTA HARMONI™ MODULAR TORIC 
INTRAOCULAR LENS SYSTEM FOR THE 
TREATMENT OF PRE-EXISTING CORNEAL ASTIGMATISM AND 
APHAKIA FOLLOWING CATARACT 
1 
TITLE PAGE 
Protocol Number:  
ClarVista CP-00004 / NCT03050697 
Medical Specialty: 
Surgical 
Project Name /Number: 
NA 
Sponsor Name & Address: 
CLARVISTA MEDICAL, INCORPORATED 
26800 ALISO VIEJO PARKWAY, SUITE 120 
ALISO VIEJO, CA 92656 
PHONE +001 949 916-5412 
FAX +001 949 916-5412 
Test Article(s) / Product(s): 
ClarVista HARMONI® Modular Toric Intraocular Lens 
System 
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CLARVISTA MEDICAL 
Rev 01, 06 June 2016                                                                        Confidential                         Page 1 of 40
 
 
 
 
 
 
 
 
 
A PROSPECTIVE, MULTI CENTER STUDY TO EVALUATE THE SAFETY AND PERFORMANCE OF THE 
EXCHANGEABLE CLARVISTA HARMONI™ MODULAR TORIC INTRAOCULAR LENS SYSTEM FOR THE 
TREATMENT OF PRE EXISTING CORNEAL ASTIGMATISM AND APHAKIA FOLLOWING CATARACT 
SURGERY  
Protocol Number  
 
  
#CP-00004 REV.01 
Sponsor 
 
 
 
 
CLARVISTA MEDICAL, INCORPORATED  
26800 ALISO VIEJO PARKWAY, SUITE 120 
ALISO VIEJO, CA 92656 
PHONE +001 949 916-5412 
FAX +001 949 916-5412 
Original Version Date (Rev.01) 
06 June 2016  
 
Th s c n ca  nvest gat on s be ng conducted n accordance w th 21 CFR Parts 11, 50, 54, 56, and 812, SO 14155 
(2011) C n ca  nvest gat on of Med ca  Dev ces for Human Sub ects, SO 11979 7:2014 Ophtha m c mp ants — 
ntraocu ar enses — Part 7, : C n ca  nvest gat ons (where app cab e), ANS  Z80 7 2013 Ophtha m c Opt cs – 
ntraocu ar Lenses (where app cab e), CH GCPs, and app cab e oca  regu at ons  
CONFIDENTIAL 
The nformat on n th s document s conf dent a  and w  not be d sc osed to others w thout wr tten author zat on 
from C arV sta Med ca , except to the extent necessary to obta n nformed consent from persons nvo ved n the 
c n ca  study or the r ega  guard ans, or for d scuss ons w th oca  regu atory author t es, nst tut ona  rev ew boards 
( RB), Eth cs Comm ttees (EC) or persons part c pat ng n the conduct of the tr a  
 
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CLARVISTA MEDICAL 
Rev 01, 06 June 2016                                                                        Confidential                         Page 2 of 40
 
 
PROTOCOL CONTACTS 
Sponsor 
ClarVista Medical 
26800 Aliso Viejo Parkway, Suite 120 
Aliso Viejo, CA 92656 
Ph: +001.949.916.5412 
Fax: +001.949.916.5412 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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CLARVISTA MEDICAL 
Rev 01, 06 June 2016                                                                        Confidential                         Page 3 of 40
 
 
 
PROTOCOL APPROVAL 
 
A Prospect ve, Mu t -Center Study to Eva uate the Safety and Performance of the C arV sta 
HARMONI® Modu ar Tor c Intraocu ar Lens System for the Treatment of Pre-Ex st ng Cornea  
Ast gmat sm and Aphak a Fo ow ng Cataract Surgery 
 
The fo ow ng nd v dua s approve Protoco  #CP-00004 Rev.01 dated 6 June 2016. Any changes to 
th s vers on of the protoco  must have an amendment or adm n strat ve etter. 
 
C arV sta Approva s: 
 
 
 
 
 
 
 
 
 
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CLARVISTA MEDICAL 
Rev 01, 06 June 2016                                                                        Confidential                         Page 4 of 40
 
 
STUDY ACKNOWLEDGEMENT 
 
I understand th s protoco  conta ns nformat on that s conf dent a  and propr etary to C arV sta 
Med ca  (C arV sta). 
I have read th s protoco  and agree that t conta ns a  the deta s necessary to conduct the study 
as descr bed. I w  fo ow th s protoco  n the conduct of the study and w  make a reasonab e 
effort to comp ete the study n the t me noted. 
I w  prov de the contents of th s protoco  to study staff under my d rect superv s on n order to 
conduct the study. I w  d scuss th s nformat on w th the study staff to ensure they are fu y 
nformed about the study and the test art c e. I w  prov de the contents of the protoco  to the 
respons b e Eth cs Comm ttee. These d sc osures may be made; prov d ng the contents are not 
used n any other c n ca  study and they are not d sc osed to any other person or ent ty w thout 
pr or wr tten consent from C arV sta. Th s cond t on does not app y to d sc osure requ red by 
government regu at ons or aws; however, I agree to g ve prompt not ce to C arV sta of any such 
d sc osure. 
I understand the study may be term nated or enro ment suspended at any t me by C arV sta, w th 
or w thout cause, or by me f t becomes necessary to protect the nterests of the study subjects. 
Any add t ona  nformat on added to th s protoco  s a so conf dent a  and propr etary to C arV sta 
and must be treated n the same manner as the contents of th s protoco . 
 
___________________________________ 
Pr nted Name of Pr nc pa  Invest gator 
___________________________________ 
 
_____________________ 
Invest gator S gnature  
 
 
 
Date 
Protoco  # CP-00004 Rev.01 
Date: 06 June 2016 
 
 
 
 
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CLARVISTA MEDICAL 
Rev 01, 06 June 2016                                                                        Confidential                         Page 5 of 40
 
 
Table of Contents 
 
1 
PROTOCOL CONTACTS ............................................................................................................................................. 2 
PROTOCOL APPROVAL ............................................................................................................................................. 3 
STUDY ACKNOWLEDGEMENT .................................................................................................................................. 4 
TABLE OF FIGURES .................................................................................................................................................. 7 
LIST OF ABBREVIATIONS ......................................................................................................................................... 7 
PROTOCOL SYNOPSIS ............................................................................................................................................... 9 
1.0 INTRODUCTION ................................................................................................................................................. 15 
2.0 OBJECTIVES ...................................................................................................................................................... 17 
3.0 STUDY DESIGN .................................................................................................................................................. 17 
3 1 
DESCR T ON O  THE STUDY 
 17 
3 2 
STUDY PO ULAT ON 
 17 
3 2 1 
nc us on Cr ter a 
 17 
3 2 2 
Exc us on Cr ter a Pr or to Surgery 
 18 
3 2 3 
D scont nuat on Cr ter a Dur ng Surgery 
 19 
3 3 
STUDY V S TS 
 20 
3 3 1 
Pre Operat ve V s t – Screen ng/Base ne (Day 90 to Day 0) 
 20 
3 3 2 
Day 0 V s t (Cataract Surgery and OL mp antat on) 
 20 
3 3 3 
Post Operat ve V s ts (Days 1 – 60) 
 21 
3 3 4 
3 Month V s t (Day 80 100) 
 21 
3 3 5 
Unschedu ed V s ts 
 21 
3 3 6 
M ssed V s ts 
 22 
4.0 
STUDY METHODS ..................................................................................................................................... 22 
4 1 
N ORMED CONSENT 
 22 
4 2 
ASS GNMENT O  SUBJECT DENT
CAT ON 
 22 
4 3 
SCREEN FA LURE 
 23 
4 4 
SUBJECT COM LET ON 
 23 
4 5 
SUBJECT D SCONT NUAT ON 
 23 
4 6  
LOST TO FOLLOW U  
 23 
4 7 
STUDY COM LET ON 
 24 
4 7 1 
Ear y Study Term nat on 
 24 
4 8 
CONCOM TANT THERA ES 
 24 
4 8 1 
Concom tant Med cat on 
 24 
4 8 2 
Concom tant Procedures 
 24 
4 9 
PROTOCOL DEV AT ONS 
 25 
5.0 
STUDY MATERIALS .................................................................................................................................. 25 
5 1 
DESCR T ON O  TEST ART CLE 
 25 
5 1 1 
nstruct ons for Use 
 26 
5 2 
PACKAG NG AND LABEL NG 
 26 
5 3 
ACCOUNTAB L TY 
 26 
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Rev 01, 06 June 2016                                                                        Confidential                         Page 6 of 40
 
 
5 4  
OTHER MATER ALS 
 27 
6.0 
ADVERSE EVENTS .................................................................................................................................... 27 
6 1 
DE N T ONS 
 27 
6 1 1 
Adverse Event (AE) 
 27 
6 1 2 
Adverse Dev ce Effect (ADE) 
 28 
6 1 3 
Unant c pated Adverse Dev ce Effect (UADE) 
 28 
6 1 4 
Dev ce Def c enc es (DD) 
 29 
6 2 
AE EVALUAT ON 
 29 
6 2 1 
Eva uat on 
 29 
6 3 
RE ORT NG 
 31 
6 3 1 
On S te Exped ted Report ng 
 31 
6 3 2 
Off S te SAE Report ng 
 32 
6 3 3 
Report ng of Comp a nts for Anc ary Marketed Products 
 32 
6 3 4 
Adverse Events and Ser ous Adverse Events at Sub ect Ex t 
 32 
6 4 
SA ETY MON TOR NG AND REV EW 
 32 
7.0  
STUDY OUTCOMES ................................................................................................................................... 32 
7 1 
SA ETY OUTCOMES 
 32 
7 2 
PER ORMANCE OUTCOMES 
 32 
 
 
8.0 
STATISTICAL METHODS .......................................................................................................................... 33 
8 1 
SAM LE S ZE CALCULAT ON 
 33 
8 2 
ANALYSES PO ULAT ONS 
 34 
8 2 1 
Safety Popu at on 
 34 
8 2 2 
mp anted Eye Popu at on 
 34 
8 2 3 
Per Protoco  Popu at on 
 34 
 
 
8 3 
STAT ST CAL METHODS 
 35 
8 3 1 
Safety Outcomes 
 35 
8 3 2 
Performance Outcomes 
 35 
 
 
9.0 
DATA MANAGEMENT ............................................................................................................................... 37 
9 1 
DATA QUAL TY ASSURANCE 
 37 
9 1 1 
Data Mon tor ng 
 37 
9 2 
RECORD RETENT ON 
 38 
10.0 
REFERENCES ............................................................................................................................................ 38 
APPENDIX A – TABLE 1: SCHEDULE OF ASSESSMENTS ......................................................................................... 40 
 
 
 
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Rev 01, 06 June 2016                                                                        Confidential                         Page 7 of 40
 
 
TABLE OF FIGURES 
F GURE 1  COHORT SCHEDULE 
 10 
F GURE 2  COHORT SCHEDULE 
 17 
F GURE 3  THE HARMON ™ MODULAR NTRAOCULAR LENS (HM OL) SYSTEM 
 26 
 
LIST OF ABBREVIATIONS 
Abbreviation/Acronym  Term  
AE  Adverse Event 
ACD Anter or Chamber Depth 
ADE  Adverse Dev ce Effect 
AL Ax a  Length 
ANSI Amer can Nat ona  Standards Inst tute 
BCDVA Best-Corrected D stance V sua  Acu ty 
CFR Code of Federa  Regu at ons 
D D opter 
DD Dev ce Def c enc es 
DFE D ated Fundus Exam nat on 
EC Eth cs Comm ttee 
eCRF E ectron c Case Report Form 
ETDRS Ear y Treatment D abet c Ret nopathy Study (Chart) 
EtO Ethy ene ox de 
FDA Un ted States Food and Drug Adm n strat on 
GCPs Good C n ca  Pract ces 
HIPAA Hea th Insurance Portab ty and Accountab ty Act 
HMTIOL HARMONI™ Modu ar Tor c Intraocu ar Lens System 
IB Invest gator Brochure 
ICF Informed Consent Form  
ICH Internat ona  Conference on Harmon zat on 
ID Ident f cat on 
IDE Invest gat ona  Dev ce Exempt on 
OA ntraoperat ve Aberrometry 
IOL Intraocu ar Lens 
IOP Intraocu ar Pressure 
IRB Inst tut ona  Rev ew Board 
ISO Internat ona  Organ zat on for Standard zat on 
K Keratometry 
LASIK Laser In-S tu Keratom eus s 
MR Man fest Refract on 
MRCYL Man fest Refract on Cy nder 
MRSE Man fest Refract on Spher ca  Equ va ent 
Nd:YAG Neodym um:Yttr um-a um num-garnet 
ND Not Done 
OD R ght Eye 
OS Left Eye 
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Rev 01, 06 June 2016                                                                        Confidential                         Page 8 of 40
 
 
OVD Ophtha m c V scoe ast c Dev ce 
PCO Poster or Capsu e Opac f cat on 
PE Pred ct on Error 
PH P nho e 
PMA Premarket Approva  
PP Per Protoco  
PRK Photorefract ve Keratectomy 
RRE Res dua  Refract ve Error 
SAE Ser ous Adverse Event 
SIA Surg ca y Induced Ast gmat sm  
SLE S t Lamp Exam nat on 
SOC Standard of Care 
SPK Superf c a  Punctate Kerat t s 
SSI Secondary Surg ca  Intervent on 
TRRE Target Res dua  Refract ve Error 
UCDVA Uncorrected D stance V sua  Acu ty 
US Un ted States 
VA V sua  Acu ty 
NOTE: 
The f rst occurrence of some abbrev at ons are not spe ed out n the document (e g  un ts of measure)  
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                                                                                                    PROTOCOL CP 00004 REV 01 
 
Rev 01, 06 June 2016                                                                        Confidential                         Page 9 of 40
 
 
PROTOCOL SYNOPSIS 
Protocol Number 
#CP-00004 Rev.01 
Title 
A Prospect ve, Mu t -Center Study to Eva uate the Safety and Performance of 
the C arV sta HARMONI® Modu ar Tor c Intraocu ar Lens System For The 
Treatment Of Pre-Ex st ng Cornea  Ast gmat sm and Aphak a Fo ow ng 
Cataract Surgery 
Regulatory Status 
Phase 4 n CE countr es 
US - Pre-IDE 
Investigational Device 
C arV sta HARMON  Modu ar Tor c ntraocu ar Lens System (HMT OL) 
Objectives 
A study to eva uate the safety and performance of the HMTIOL n pat ents 
w th pre-ex st ng cornea  ast gmat sm. Spec f ca y,  
• 
To ref ne the A-constant ( ens constant) of the HMTIOL. 
• 
To eva uate the refract ve outcomes nc ud ng ast gmat sm correct on 
w th HMTIOL n pr mary cataract surgery. 
• 
To eva uate ax a  and rotat ona  stab ty of the HMTIOL 
Number of Clinical Sites 
and Study Subjects 
Up to 200 enro ed and mp anted eyes from up to 10 nvest gat ona  s tes. 
Approx mate y 20 eyes, a max mum of 30, w  be enro ed from each 
nvest gator/surgeon. Enro ment w  be mon tored as out ned n Samp e S ze 
sect on and adjusted accord ng y.  
Study Duration 
A  subjects w  part c pate n the study for up to 6 months (3 months pre-op 
w ndow p us 3 months fo ow up per od). 
Tota  study durat on w  be approx mate y 9 months. 
Study Design 
Prospect ve, mu t -center c n ca  study. 
A  subjects w  be seen for a Preoperat ve V s t to capture base ne 
measurements. One or both eyes of each subject w  undergo cataract surgery 
and be mp anted w th the HMTIOL. Eyes w th cornea  ast gmat sm wh ch s 
w th n the d optr c range of the tor c IOL (1.50, 2.25 and 3.00D at the IOL p ane 
after adjust ng for Surg ca y Induced Ast gmat sm) may be mp anted w th the 
study dev ce. 
Fo ow up:  
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                                                                                                    PROTOCOL CP 00004 REV 01 
 
Rev 01, 06 June 2016                                                                        Confidential                         Page 11 of 40
 
 
2. Rate of dev ce-re ated Secondary Surg ca  Intervent on’s (SSI’s) other 
than opt c exchange or rotat ona  adjustment of the HMTIOL 
3. Dev ce def c ency 
4. AEs rates  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion Exclusion Criteria 
*both eyes do not need to 
be eligible 
Inc us on cr ter a 
1. Adu t at east 22 years of age at the t me of consent 
2. Must be w
ng and ab e to return for schedu ed treatment and fo ow-
up exam nat ons for up to 6 months study durat on  
3. P anned remova  of v sua y s gn f cant cataract (cort ca , nuc ear, 
poster or subcapsu ar, or a comb nat on) by manua  
phacoemu s f cat on cataract extract on 
4. Pre-ex st ng cornea  ast gmat sm n the study eye. Magn tude of 
ast gmat sm w th n the range of ava ab e tor c power 1.50, 2.25 and 
3.00D at the IOL p ane, after adjust ng for Surg ca y Induced 
Ast gmat sm. 
5. Target d optr c ens power w th n the range of 16 – 26D 
6. Must be w
ng to d scont nue contact ens wear for the durat on of the 
study and demonstrate refract ve stab ty pr or to b ometry and 
surgery  
NOTE: Due to potent a  var ab ty of VA and MR outcomes fo ow ng gas 
permeab e (GP) contact ens wear, a  subjects who have worn GP 
contact enses must comp ete the consent ng process, d scont nue wear 
for 3 weeks and exh b t a stab e Man fest Refract on (as ev denced by 
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                                                                                                    PROTOCOL CP 00004 REV 01 
 
Rev 01, 06 June 2016                                                                        Confidential                         Page 12 of 40
 
 
two MR eva uat ons at east 1 week apart resu t ng n ≤0.50D MRSE 
d fference n the two refract ons) and Keratometry read ngs (as 
ev denced by two K read ngs at east 1 week apart resu t ng n ≤0.50D 
d fference between the two read ngs) pr or to f na  IOL ca cu at ons. 
S m ar y, any subjects who current y wear soft contact enses must a so 
comp ete the consent ng process, d scont nue wear for a m n mum of 1 
week and return for repeat e g b ty test ng exh b t stab e MR and K 
read ngs. In add t on, a  qua fy ng subjects must d scont nue contact 
ens wear n the study eye for the durat on of study part c pat on. 
7. BCVA projected to be 0.2 LogMAR or ower (as determ ned by the 
med ca  judgment of the Invest gator or measured by potent a  acu ty 
meter / ret na  acu ty meter (PAM / RAM) f necessary) 
8. V sua  symptoms re ated to cataract 
9. Stab ty of the cornea has been demonstrated by keratometry 
10. D ated pup  s ze at east 7.0mm 
11. Must be ab e to understand and prov de nformed consent themse ves 
or through a representat ve w th a w tness present on the IRB or EC 
approved Informed Consent Form (ICF) 
Exc us on cr ter a 
1. H story of any ntraocu ar or cornea  surgery n study eye ( nc ud ng 
refract ve) 
2. Any type of cataract (e.g. traumat c, congen ta , po ar) other than those 
noted n nc us on cr ter a 
3. Pregnancy or actat on 
4. Part c pat on n any other drug or dev ce c n ca  tr a  w th n 30 days 
pr or to enro ng n th s study and/or dur ng study part c pat on 
5. Prev ous cornea based surgery (LASIK, PRK, LRI, etc.) 
6. H story of any c n ca y s gn f cant ret na  patho ogy or ocu ar d agnos s 
(e.g. d abet c ret nopathy, schem c d seases, macu ar degenerat on, 
ret na  detachment, amb yop a, opt c neuropathy, etc.) n study eye 
that cou d a ter or m t f na  postoperat ve v sua  prognos s 
7. H story of any ocu ar cond t ons wh ch cou d affect the stab ty of the 
IOL (e.g. pseudoexfo at on, zonu ar d a ys s, ev dent zonu ar weakness 
or deh scence, etc.) n study eye 
8. Any anter or segment patho ogy ke y to ncrease the r sk of 
comp cat ons from phacoemu s f cat on cataract extract on (e.g. 
chron c uve t s, r t s, r docyc t s, an r d a, rubeos s r d s, c n ca y 
s gn f cant cornea , Fuch’s, or anter or membrane dystroph es, etc.) n 
study eye 
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For categor ca  outcomes, the counts and percentages of eyes w th each 
categor ca  eve  of outcome w  be summar zed.   
The cumu at ve and pers stent adverse events w  be summar zed at 3 months 
   
For BCDVA and UCDVA, the number and percentages of eyes w th v sua  acu ty 
of 20/20 or better 20/25 or better, 20/32 or better, 20/40 or better, and worse 
than 20/40 at each v s t w  be summar zed. 
The MRSE pred ct on error w  be ca cu ated for each eye (Sect on 8) and 
summar zed us ng stat st cs for cont nuous var ab es.  The MRCYL pred ct on error 
(per cy nder power and vector ana ys s) w  be der ved for eye w th HMTIOL and 
summar zed us ng stat st cs for cont nuous var ab es.  
 
  The 
reduct on n MRCYL (abso ute power) and the percent reduct on n cy nder 
power w  be der ved for each eyes mp anted w th HMTIOL.  Reduct ons w  be 
summar zed us ng stat st cs for cont nuous var ab es.  Add t ona  vector ana yses 
on MRCYL may be prov ded. 
IOL rotat on w  be der ved for each eye from Day 0 (surgery) to postoperat ve 
v s ts.  The stat st cs for cont nuous var ab es w  be prov ded.  The number and 
percentage of eyes w th rotat on of £ 5 , < 10 , < 20 , and < 30  w  be ca cu ated.  
 
 
 
 
 
 
 
 
 
 
 
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                                                                                                    PROTOCOL CP 00004 REV 01 
 
Rev 01, 06 June 2016                                                                        Confidential                         Page 15 of 40
 
 
1.0 INTRODUCTION 
Cataract surgery s a m n ma y nvas ve procedure des gned to restore v s on w th short recovery t me.  Advances n 
nstrumentat on and techn ques over the past few decades have fac tated the enhancement n safety1 wh e a ow ng 
for reproduc b e outcomes.  Wh e the ser ous adverse event rate rema ns ow, se ect ng the r ght ntraocu ar ens 
(IOL) mp ant for spectac e ndependence rema ns an on-go ng cha enge.  Th s s referred to as res dua  refract ve 
error (RRE) and typ ca y nvo ves approx mate y 0.6 d opters (D)2 of uncorrected focus ng power.  Furthermore, t s 
reported that current b ometry measurements for se ect ng the correct IOL and subsequent surg ca  methods are 
assoc ated w th: 
1. Up to 16% of pat ents undergo ng add t ona  surg ca  correct on to ach eve 20/20 unass sted v s on2. 
2. Up to 55% of pat ents fa ng outs de of the r targeted postoperat ve refract on by at east 0.5D3,4,5. 
3. Between 14 and 24% of surger es resu t n greater than 1 D of res dua  refract ve error, when us ng 
manufacturer suggested constants3.  
4. Up to 6% of pat ents exper ence un ntended and s gn f cant post-operat ve rotat on of a tor c IOL4. 
Rotat ons between 5-40 degrees have been observed and for every 1 degree of rotat on, 3% of the 
correct ve power of the tor c surface s ost. 
 
Pat ents are frequent y sat sf ed w th the resu ts of the r cataract surgery and enjoy re at ve y qu ck recovery w th 
restorat on of v s on. However, as expectat ons have evo ved over t me, pat ents are demand ng the same degree of 
spectac e ndependence that other refract ve surger es such as LASIK prov de.  Current y ava ab e opt ons to he p 
ach eve spectac e ndependence when RRE s present nc ude: contact enses, cornea  mod f cat on (surgery or other), 
IOL exchange/man pu at on, or su cus p acement of a “p ggyback” IOL.  These a ternat ves have s gn f cant m tat ons 
and r sks. 
Comp cat ons due to contact enses are rare; however, contact ens nto erance and contact ens-re ated nfect ons 
cou d be ser ous and s ght threaten ng. For some pat ents, contact ens wear s contra nd cated and they must resort 
to the use of spectac es.  E der y pat ents n part cu ar have d ff cu ty hand ng contact enses.  
If the pat ent s w
ng to accept the add t ona  cost and r sks of a secondary procedure, the phys c an has more 
opt ons; however, each of them poses a s gn f cant r sk to the pat ent as out ned be ow.  
Corneal modifications have been performed on tens of m
ons of peop e across the wor d w th some form of 
refract ve surgery (e.g. LASIK).  For examp e, n the U.S. (where the most extens ve data ex sts) 11.5M Amer cans have 
had cornea  refract ve surgery and over the next two decades many w  need cataract surgery.   LASIK ncreases the 
ke hood for res dua  refract ve error post cataract surgery due to naccurate IOL power ca cu at ons w th b ometry.  
There s hes tat on among many ophtha mo og sts to repeat LASIK for RRE after cataract surgery because the FDA has 
not spec f ca y eva uated the safety and effect veness of repeated LASIK n th s sett ng.  A  the r sks assoc ated w th 
the or g na  LASIK procedure app y to retreatment, a ong w th the ncreased potent a  for ep the a  ngrowth, cornea  
ectas a and ess robust nomograms for IOL se ect on for post cataract pat ents.   
Furthermore, even for eyes that have not undergone pr or cornea  refract ve surgery, the FDA has not spec f ca y 
eva uated the safety and effect veness of cornea  refract ve procedures (e.g., ast gmat c keratotomy, LASIK, PRK, etc.) 
to address RRE fo ow ng ens rep acement surgery, so the use of approved asers for th s purpose n the U.S. s 
cons dered off- abe  and the r sks are not we  character zed.  For examp e, t s unc ear how opt ca  aberrat ons that 
m ght be present w th an IOL n p ace are ncreased by aberrat ons nduced by cornea  refract ve procedures, how 
ke y cornea  refract ve procedures are to nduce rregu ar ast gmat sm and worsen dry eye that s nduced by cataract 
surgery, and whether cornea  refract ve procedures cou d create potent a  comp cat ons re ated to cataract surgery 
wound hea ng or IOL stab ty.   
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Furthermore, cornea based ntervent ons do not address the root cause of RRE after cataract extract on ( mprec se 
IOL power se ect on) and expose the pat ent to a new and ndependent set of poss b e adverse events.  Thus, t wou d 
be des rab e to be ab e to correct or mod fy the opt ca  resu t w thout the need to rrevers b y and unpred ctab y a ter 
cornea  t ssue fo ow ng cataract extract on. 
Sulcus placement of a “piggyback” IOL s a procedure that has not been eva uated for safety and effect veness by the 
FDA so the use of approved IOLs for th s purpose n the U.S. s off- abe .  Among the comp cat ons reported w th th s 
procedure are secondary p gment d spers on, r s/pup  rregu ar t es, chron c r t s, hyphema, g aucoma, zonu ar 
d srupt on and/or poster or capsu ar rupture.  Thus, t wou d be des rab e to be ab e to correct or mod fy the opt ca  
resu t w thout the need to mp ant a “p ggyback” IOL w th ts nherent ser ous r sks. 
IOL Exchange/Manipulation n genera , s techn ca y cha eng ng for the surgeon and poses an atrogen c r sk to 
ntraocu ar structures nc ud ng the ens capsu e, r s, and endothe um of the cornea.  The capsu ar bag f broses weeks 
after IOL mp antat on creat ng a strong adhes on between the capsu e and the IOL. Man pu at on of the capsu ar bag 
to remove an IOL s the major r sk n th s sett ng and can damage the capsu ar bag nc ud ng poster or capsu ar rupture 
and capsu ar bag d s ocat on. The capsu ar bag cannot be repa red once damaged. Th s r sk ncreases over t me as the 
capsu ar bag adheres to the IOL and hapt cs. Even when IOL exchange s not requ red, man pu at on of trad t ona  IOL’s 
to rotate or center the opt c ntroduces the r sk of capsu ar or zonu ar damage wh ch can cause further ens nstab ty 
and ens ma pos t on.  Thus, t wou d be des rab e to be ab e to correct RRE w thout the need to remove the ent re IOL 
part cu ar y after capsu ar contract on or f bros s. 
The C arV sta Harmon TM Modu ar IOL System s a CE-approved dev ce des gned for safe and easy post-operat ve 
adjustment of res dua  refract ve error (RRE). The modu ar IOL concept w  serve as a va uab e add t on to the 
armamentar um of cataract surgeons. The goa  of th s techno ogy s to mprove refract ve (spher c and tor c) outcomes 
and avo d the s gn f cant r sks of secondary procedures current y be ng performed as standard pract ce to address RRE 
n an nd rect manner. It s ant c pated that th s modu ar ens w  prov de c n ca  ut ty n two bas c areas, the f rst 
be ng the focus of th s study. 
1. Post-operat ve correct on of res dua  spher ca  refract ve error – Based on ex st ng performance of 
convent ona  cataract surgery, researchers have conc uded that refract ve outcomes n norma  eyes shou d 
be w th n 0.5D for 45% and w th n 1D for 85% of cataract cases5.  Th s theoret ca  performance goa  st  
fa s substant a y short of the rea -wor d outcomes seen w th cornea  refract ve surgery and wh ch cataract 
pat ents and surgeons ncreas ng y demand. As a consequence, secondary procedures to opt m ze v sua  
outcomes fo ow ng cataract surgery can be as h gh as 16% n some pract ces, part cu ar y for prem um ens 
pat ents2.    
Modu ar IOL techno ogy s ntended to d rect y mprove refract ve outcomes w thout the nherent r sk of a 
fu  ens exchange or resort ng to the use of a cornea  refract ve aser.  W th the HARMONI™ des gn the 
spher ca  opt c component s ntended to a ow exchange for a d fferent power opt c or adjusted to a gn 
w th the v sua  ax s w thout extens ve man pu at on of the de cate capsu ar bag, thereby avo d ng the 
potent a  for ntraocu ar (e.g., capsu ar and endothe a ) trauma that s seen w th trad t ona  IOL exchanges. 
2. Post-operat ve correct on of rotat ona y d sp aced or off-ax s tor c ens – For every 1 degree a tor c IOL ax s 
s off from the true postoperat ve ax s of ast gmat sm, there w  be a 3.3% oss of tor c correct on.  Study 
data support ng a recent approva  of a tor c IOL (P930014/S045) showed that 6.7% of eyes underwent a 
secondary surg ca  ntervent on (SSI) n the form of IOL repos t on ng to reso ve RRE.  The HARMONI™ 
modu ar techno ogy can be used to mprove outcomes n pat ents where the tor c ens has been d sp aced 
to an un ntended pos t on dur ng the post-operat ve per od.  The HARMONI™ opt c a ows for adjustment 
to a gn w th the ast gmat c mer d an or v sua  ax s w thout man pu at on of the base component thereby 
avo d ng the potent a  for capsu ar trauma that s seen when tor c IOLs are man pu ated n the post-
operat ve per od. 
The C arV sta Harmon TM Monofoca  (non-tor c) Modu ar IOL System has been ava ab e s nce 2015. A tor c vers on, 
the C arV sta Harmon TM Tor c Modu ar IOL System (HMTIOL), has been recent y CE-approved. 
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2. Must be w
ng and ab e to return for schedu ed treatment and fo ow-up exam nat ons for up to 6 month 
study durat on, per eye. 
3. P anned remova  of v sua y s gn f cant b atera  cataract (cort ca , nuc ear, poster or subcapsu ar, or a 
comb nat on) by manua  phacoemu s f cat on cataract extract on 
4. Pre-ex st ng cornea  ast gmat sm n at east 1 eye. Magn tude of ast gmat sm 0.75 to 2.50D of cornea  
ast gmat sm (w th n the range of ava ab e tor c power 1.50, 2.25 and 3.00D at the IOL p ane after adjust ng 
for Surg ca y Induced Ast gmat sm) 
5. Target d optr c ens power w th n the range of 16 – 26D 
6. Must be w
ng to d scont nue contact ens wear for the durat on of the study and demonstrate refract ve 
stab ty pr or to b ometry and surgery 
NOTE: Due to potent a  var ab ty of VA and MR outcomes fo ow ng gas permeab e (GP) contact ens wear, 
a  subjects who have worn GP contact enses must comp ete the consent ng process, d scont nue wear for 3 
weeks and exh b t a stab e Man fest Refract on (as ev denced by two MR eva uat ons at east 1 week apart 
resu t ng n ≤0.50D MRSE d fference n the two refract ons) and Keratometry read ngs (as ev denced by two 
K read ngs at east 1 week apart resu t ng n ≤0.50D d fference between the two read ngs) pr or to f na  IOL 
ca cu at ons. S m ar y, any subjects who current y wear soft contact enses must a so comp ete the 
consent ng process, d scont nue wear for a m n mum of 1 week and return for repeat e g b ty test ng 
exh b t stab e MR and K read ngs. In add t on, a  qua fy ng subjects must d scont nue contact ens wear n 
the study eye for the durat on of study part c pat on. 
7. BCVA projected to be 0.2 LogMAR or ower (as determ ned by the med ca  judgment of the Invest gator or 
measured by potent a  acu ty meter / ret na  acu ty meter (PAM / RAM) f necessary) 
8. V sua  symptoms re ated to cataract 
9. Stab ty of the cornea has been demonstrated by keratometry 
10. D ated pup  s ze at east 7.0mm 
11. Must be ab e to understand and prov de nformed consent themse ves or through a representat ve w th a 
w tness present on the IRB or EC approved Informed Consent Form (ICF) 
 
3.2.2 EXCLUS ON CR TER A PR OR TO SURGERY 
1. H story of any ntraocu ar or cornea  surgery n study eye ( nc ud ng refract ve) 
2. Any type of cataract (e.g. traumat c, congen ta , po ar) other than those noted n nc us on cr ter a 
3. Pregnancy or actat on 
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4. Part c pat on n any other drug or dev ce c n ca  tr a  w th n 30 days pr or to enro ng n th s study and/or 
dur ng study part c pat on 
5. Prev ous cornea based surgery (LASIK, PRK, LRI, etc.) 
6. H story of any c n ca y s gn f cant ret na  patho ogy or ocu ar d agnos s (e.g. d abet c ret nopathy, schem c 
d seases, macu ar degenerat on, ret na  detachment, amb yop a, opt c neuropathy, etc.) n study eye that 
cou d a ter or m t f na  postoperat ve v sua  prognos s 
7. H story of any ocu ar cond t ons wh ch cou d affect the stab ty of the IOL (e.g. pseudoexfo at on, zonu ar 
d a ys s, ev dent zonu ar weakness or deh scence, etc.) n study eye 
8. Any anter or segment patho ogy ke y to ncrease the r sk of comp cat ons from phacoemu s f cat on 
cataract extract on (e.g. chron c uve t s, r t s, r docyc t s, an r d a, rubeos s r d s, c n ca y s gn f cant 
cornea , Fuch’s, or anter or membrane dystroph es, etc.) n study eye 
9. Any v sua y s gn f cant ntraocu ar med a opac ty other than cataract n study eye (as determ ned by the 
nvest gator) 
10. Uncontro ed g aucoma n study eye (per Invest gator judgement) 
11.  Subjects w th arge refract ve errors (hyperop a/myop a) of ax a  or patho og c or g n that, n the op n on of 
the nvest gator, cou d confound outcomes 
12. Uncontro ed system c d sease (e.g. d abetes me tus, act ve cancer treatment, menta  ness, etc)  
13. Subject who, n the c n ca  judgment of the nvest gator, s not su tab e for part c pat on n the study for 
another c n ca  reason, as documented by the nvest gator 
14. Severe dry eye that, n the op n on of the nvest gator, wou d mpa r the ab ty to obta n re ab e study 
measurements  
15. Tak ng system c med cat ons that, n the op n on of the nvest gator, may confound the outcome or ncrease 
the ntraoperat ve and post-operat ve r sk to the subject (e.g. Tamsu os n Hydroch or de – F omax) or other 
med cat ons nc ud ng ant cho nerg cs, a pha adrenerg c b ock ng agents w th s m ar s de effects (e.g. sma  
pup /f oppy r s syndrome) 
3.2.3 D SCONT NUAT ON CR TER A DUR NG SURGERY 
1. V treous oss pr or to use of the nvest gat ona  dev ce 
2. Pos t ve poster or pressure prevent ng safe mp antat on of the ens system 
3. Anter or chamber hyphema prevent ng v sua zat on of mp antat on 
4. Any zonu ar or capsu ar rupture or capsu ar bag nstab ty 
5. Intraoperat ve m os s prevent ng v sua zat on of f xat on features 
6. Need for concom tant procedures (e.g. g aucoma surgery, LRI, RK, LASIK, etc.) 
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7. Subject who, n the c n ca  judgment of the nvest gator, s not su tab e for part c pat on n the study for 
another c n ca  reason, as documented by the nvest gator 
3.3 
STUDY VISITS 
The t m ng and frequency of each assessment to be performed at each v s t, w  be carr ed out accord ng to “Append x 
A – Schedu e of Assessments.”   
Procedures to be fo owed n order to carry out each nd v dua  assessment, are under separate cover (See study 
spec f c Manua  of Procedures).  
In a  nstances for those subjects w th both eyes enro ed, f the f rst study eye and secondary eye post-operat ve 
assessments cannot be seen on the same day and both rema n “ n-w ndow,” the subject must return for a separate 
v s t n order to ma nta n “ n-w ndow” status for both eyes throughout study part c pat on. 
3.3.1 PRE-OPERAT VE V S T – SCREEN NG/BASEL NE (DAY -90 TO DAY 0) 
After prov d ng nformed consent (see Sect on 4.1), prospect ve subjects w  be screened to determ ne 
whether they meet enro ment cr ter a. Demograph c nformat on, re evant ocu ar h story, and current ocu ar 
med cat on use w  be co ected. If a  cr ter a are met, the subject w  be cons dered enro ed, IOL ca cu at on 
comp eted to determ ne appropr ate HMTIOL power, and the subject schedu ed for surgery. 
3.3.2 DAY 0 V S T (CATARACT SURGERY AND IOL IMPLANTAT ON)  
Record any changes n concom tant med cat ons and med ca  h story, prepare the subject for surgery n the 
study eye (see Surg ca  Procedure Gu de), and re-rev ew nc us on/exc us on cr ter a to ensure subject st  
qua f es to part c pate.  
The Invest gator w  carry out the surg ca  procedure and HMTIOL mp antat on as spec f ed n the Surg ca  
Procedure Manua  and the fo ow ng deta s w  be captured n both Source Documents and eCRFs: 
• 
Date of surgery 
• 
Operat ve eye 
• 
Inc s on ocat on and s ze 
• 
Ophtha m c V scoe ast c Dev ce (OVD) used  
• 
A  med cat on used pre-, ntra-, and post-operat ve y (ophtha m c and system c) 
• 
Mode , ser a  number, and d opter of HMTIOL mp ant components 
• 
Tor c IOL power and ax s or entat on  
• 
IOL nject on dev ce  
Once the subject s conf rmed stab e post-surgery, prov de IRB / EC approved post-operat ve nstruct ons and 
d scharge.  
Record any AEs, adverse dev ce effects (ADEs), unexpected adverse dev ce effects (UADEs), or dev ce 
def c enc es (DD) (see Sect ons 6.1.1, 6.1.2, 6.1.3, or 6.1.4 respect ve y) observed pre-, ntra-, or post-
operat ve y. 
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In the event the subject s not mp anted w th the HMTIOL, the surgeon w  prov de the best care opt on to 
the pat ent, nc ud ng mp ant ng a commerc a y ava ab e IOL.  
In the event the subject s not mp anted w th an HMTIOL dev ce due to an ntra-operat ve comp cat on, the 
subject w  be d scont nued (see Sect on 4.5). 
3.3.3 POST-OPERAT VE V S TS (DAYS 1 – 60) 
A  subjects mp anted w th a study ens w  be seen for 1 Day, 1 Week, 1 and 3 Month assessments as out ned 
n Append x A. 
IN ADDITION, the second eye, f e g b e and enro ed n the study, w  be mp anted dur ng th s t me per od. 
It s recommended (at the f na  d scret on of the Invest gator), to comp ete th s procedure as c ose to the 1 
Week V s t (after f rst eye cataract extract on) as poss b e. S nce second eye assessments w  be comp eted 
on the same schedu e as the f rst eye assessments (see Append x A – Tab e 1), th s w  a ow the subject further 
conven ence n attend ng as many post-operat ve b atera  assessment v s ts as poss b e.  
The Invest gator w  carry out the second eye surg ca  procedure as spec f ed n the Surg ca  Procedure Manua  
and the fo ow ng deta s w  be captured n both Source Documents and eCRFs: 
• 
Date of surgery 
• 
Operat ve eye 
• 
Inc s on ocat on and s ze 
• 
Ophtha m c V scoe ast c Dev ce (OVD) used  
• 
A  med cat on used pre-, ntra-, and post-operat ve y (ophtha m c and system c) 
• 
Mode , ser a  number, and d opter of HMTIOL mp ant components 
• 
Tor c IOL power and ax s or entat on  
• 
IOL nject on dev ce 
Once the subject s conf rmed stab e post-surgery, prov de post-operat ve nstruct ons and d scharge.  
NOTE: A  concom tant med cat on, AE, and SAE co ect on must be cont nued throughout the course of the study. 
Any outcomes resu t ng n unacceptab e RRE (as determ ned between Invest gator and Subject), can be addressed 
w th spectac es, a contact ens, or surg ca  correct on. Any PO surg ca  adjustments to address RRE (cornea  refract ve 
surgery, ens exchange, ens rotat on, etc.) w  be carr ed out as determ ned to be n the best nterest of the subject. 
The course of treatment w  fo ow the Invest gators SOC and be co ected as a concom tant procedure. If surg ca  
correct on of the RRE s performed dur ng the nvest gat on per od, the refract ve error pr or to secondary surgery s 
reported as the f na  resu t. 
 
3.3.4 3 MONTH V S T (DAY 80-100) 
Assessments w  be comp eted as nd cated n Append x A – Tab es 1 and 2. In the event the second eye s out 
of w ndow at th s v s t, the subject w  return n-w ndow to comp ete second eye assessments. 
3.3.5 UNSCHEDULED V S TS  
If at any t me dur ng the study, outs de of the above schedu ed v s ts, the subject requests or the Invest gator 
determ nes the subject shou d be assessed, an unschedu ed v s t may occur. Adverse events and concom tant 
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med cat ons w  be recorded and assessments deemed necessary by the Invest gator shou d be performed on e ther 
or both eyes.  
If a subject s seen for mu t p e v s ts dur ng a g ven v s t w ndow, the data from a v s t that s ntended to meet the 
protoco  requ rements for the schedu ed v s t shou d be captured n the v s t eCRF. Where such a determ nat on cannot 
be made, the f rst v s t w th n the schedu ed v s t w ndow w  be used for comp et on of the protoco  requ red v s t. If 
assessments are m ss ng from that v s t, however captured at subsequent v s ts w th n w ndow, those assessments 
can be co ected as part of the protoco  v s t. In such a c rcumstance, the v s t date w  rema n cons stent w th the f rst 
v s t estab shed w th n the v s t w ndow, per the scenar o above. Any add t ona  and app cab e data captured and 
assoc ated w th the Study Eye w  be captured as an Unschedu ed V s t. 
3.3.6 M SSED V S TS 
If a subject m sses any schedu ed v s t and cannot be seen pr or to the start of the next v s t w ndow, the v s t 
w  be cons dered “m ssed.” 
4.0 STUDY METHODS 
Pr or to recru tment of any subjects nto the study, rev ew and wr tten approva  of the protoco  and nformed consent 
must be obta ned from the Inst tut ona  Rev ew Board (IRB) or Eth cs Comm ttee (EC) by each part c pat ng c n ca  s te.   
4.1 
INFORMED CONSENT 
Informed consent must be obta ned and documented n wr t ng pr or to the n t at on of any study procedures. The 
subject (or the subject s ega y author zed representat ve) must be a owed suff c ent t me to thorough y read (or have 
exp a ned), the nformed consent form. The Invest gator or h s/her des gnee shou d answer any quest ons that the 
subject/representat ve m ght have. If the subject agrees to part c pate n the study, ( .e. prov des nformed consent) 
the subject/representat ve must s gn two cop es of the nformed consent form. The w tness and the Invest gator must 
a so s gn both cop es of the nformed consent form. One copy of the nformed consent form shou d be g ven to the 
subject/representat ve. If app cab e, t w  be prov ded n a cert f ed trans at on of the oca  anguage. As part of the 
consent ng process, the subjects w  be nformed of the r r ght to treatment for any njur es re ated to the study. Any 
and a  such treatment f necessary, w  be pa d for by the Sponsor to the extent t s not covered by a subject’s 
hea thcare coverage (subject to oca  eth cs comm ttee approva ). Comp et on of the consent ng process as we  as the 
date of the subject’s s gnature on the nformed consent form shou d be noted n the subject’s med ca  chart.   
Subjects who comp ete the nformed consent process w  be screened for e g b ty. Screened subjects w  be 
recorded on s te-spec f c screen ng ogs and once they are determ ned as be ng e g b e, they w  be enro ed nto the 
study and an HMTIOL order p aced w th the Sponsor f necessary. A  e g b e subjects w  rece ve a st pend to attend 
schedu ed study v s ts as an a owance for food, t me, and trave  expenses. 
4.2 
ASSIGNMENT OF SUBJECT IDENTIFICATION 
A un que and sequent a  subject dent f cat on number (ID) w  be ass gned at screen ng and never dup cated for 
another subject. Th s ID w  be used on a  study-re ated documents. To ma nta n conf dent a ty, the subject’s name 
w  not be recorded on any study document other than the nformed consent form. 
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4.3 
SCREEN FAILURE 
A record of screen fa ures and the reasons for the screen fa ures w  be recorded n the subject source documents 
and captured n the eCRF for summary. 
4.4 
SUBJECT COMPLETION 
The subject has comp eted the ent re study when the HMTIOL has been mp anted and the Sponsor rece ves 
comp eted e ectron c Case Report Form (eCRF) documentat on for a  v s ts and a Study Ex t eCRF. Subjects who requ re 
further fo ow-up for an AE w  be fo owed accord ng to Sect on 6.3.4. 
A Study Ex t eCRF must be comp eted for a  subjects who comp ete the c n ca  nvest gat on. 
4.5 
SUBJECT DISCONTINUATION 
A subject MUST be d scont nued pr or to the f na  study v s t for any of the fo ow ng reasons: 
• 
Death  
• 
Subject s enro ed and schedu ed for surgery but s not mp anted w th an HMTIOL n at east one eye 
• 
Surg ca  comp cat on(s) unre ated to the nvest gat ona  dev ce prevent ng the mp antat on of the HMTIOL ( .e. 
capsu orhex s tear, zonu ar rupture, ev dent zonu ar weakness or deh scence, poster or capsu ar rupture, v treous 
oss, poster or capsu ar p aque, s gn f cant detached Descemet’s membrane, s gn f cant anter or chamber 
b eed ng, r s ncarcerat on or damage, cornea  endothe a  touch, unsuccessfu / ncomp ete phacoemu s f cat on, 
hapt c and/or opt c damage/hapt c amputat on) 
• 
Exp antat on of the HMTIOL System  
If the study ens s exp anted, one postoperat ve v s t shou d be comp eted to record best-corrected d stance v sua  
acu ty (BCDVA) before the subject s d scont nued. 
Subjects who w thdraw from the study w  be asked to comp ete procedures out ned n the 3 Month V s t ( f 
w thdrawn pr or to that v s t). Subjects who are term nated due to an AE w  be fo owed, f poss b e, at east unt  
reso ut on or stab zat on of the AE. Subject w thdrawa s w  be documented c ear y on the source document and 
app cab e eCRF. 
Pr or to d scont nu ng a subject, every effort shou d be made to contact the subject, schedu e a f na  study v s t, and 
obta n as much fo ow-up data as poss b e. Adverse events w  be fo owed as descr bed n Sect on 6.3.4. D scont nued 
subjects shou d be fo owed outs de of the study protoco  accord ng to the Invest gator’s norma  postoperat ve 
standard of care.  
A Study Ex t eCRF must be comp eted for a  subjects who d scont nue from the c n ca  nvest gat on. 
4.6  
LOST TO FOLLOW UP 
Subjects who m ss the r 3-month v s t, as def ned by the v s t w ndows and cannot be contacted, may be cons dered 
ost to fo ow-up. A  fo ow-up attempts w  be documented and kept w th the subject’s source documentat on, and 
the app cab e eCRFs w  be comp eted. 
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Subjects that vo untar y w thdraw consent after mp antat on w th the HMTIOL w  be cons dered Lost to Fo ow-Up 
and an Ex t Form w  be comp eted. 
4.7 
STUDY COMPLETION 
C arV sta w  not fy the Invest gators when to contact the IRB / EC to announce study comp et on at the s te.  
4.7.1 EARLY STUDY TERM NAT ON 
C arV sta has the r ght to term nate th s study at any t me. Reasons for term nat ng the study may nc ude, but 
are not m ted to, the fo ow ng: 
• 
The nc dence or sever ty of adverse events n th s or any ongo ng stud es nvo v ng the same techno ogy 
( f app cab e), nd cates a potent a  hea th hazard to subjects 
• 
Subject enro ment s unsat sfactory 
• 
Data record ng s naccurate or ncomp ete. 
In the event of premature study term nat on, appropr ate not f cat on w  be g ven to the Invest gators, IRB / 
ECs, and regu atory bod es as app cab e. In add t on, C arV sta (or des gnee) w  nstruct a  Invest gators to 
d scont nue d spens ng study mater a s or treatments, w  ensure a  subjects comp ete appropr ate fo ow-
up, and w  arrange study c oseout v s ts at each s te as appropr ate. 
4.8 
CONCOMITANT THERAPIES  
4.8.1 CONCOM TANT MED CAT ON 
Concom tant med cat ons are any prescr pt on drugs used by a subject unt  conc us on of study part c pat on. 
Any med cat on the Invest gator deems n the best nterest of the subject, s acceptab e to prescr be or 
adm n ster. However, any and a  are to be recorded n both the Concom tant Med cat on source document 
and eCRF as we  as the reason for use ( nd cat on). An AE s to be reported and/or recorded as appropr ate 
(see Sect on 6.0). 
4.8.2 CONCOM TANT PROCEDURES 
A concom tant procedure s any nvas ve or non- nvas ve ocu ar or per -ocu ar procedure that takes p ace 
dur ng study part c pat on and w  be captured n both the Concom tant Procedure Source Document and 
eCRF. The fo ow ng are examp es of two such procedures: 
• 
Any PO surg ca  adjustments ( .e. cornea  refract ve surgery, ens exchange, ens rotat on, etc.) 
• 
Neodym um: Yttr um-a um num-garnet (Nd:YAG) procedure to treat Poster or Capsu e Opac f cat on 
(PCO), f necessary. Th s w  be sted as “Nd:YAG Capsu otomy.” 
Note: Any Nd:YAG capsulotomy procedures prior to exit will be performed only in response to spontaneous 
subject complaints (i.e. not solicited by study personnel) of reduced Visual Acuity (VA) or glare that affects 
functional vision, which is associated with PCO or striae, and captured on the eCRF in SLE findings. 
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An AE s to be reported and/or recorded as appropr ate (see Sect on 6.0). Any procedure reported n the 
Concom tant Procedure eCRF must have a correspond ng Ind cat on sted n e ther the Ocu ar H story or AE 
eCRF (Only exception: PCO – See Section 6.1 for further details). 
4.9 
PROTOCOL DEVIATIONS 
A  protoco  dev at ons, the date of dev at on, and reason w  be documented n the Source Document and eCRF. A  
dev at ons w  be categor zed as e ther major or m nor n the fo ow ng manner: 
Major:   
• 
Dev at ons mpact ng subject safety (e.g. e g b ty)   
• 
Dev at ons mpact ng subject r ghts (e.g. consent) 
• 
Dev at ons mpact ng data ntegr ty (e.g. nstrumentat on, mask ng) 
M nor:  
• 
A  other dev at ons (e.g. out of w ndow v s ts, m ssed data po nt, etc.)  
A  major dev at ons must be reported by the Invest gator to the Sponsor and IRB/EC mmed ate y. Subject assessments 
w  cont nue per protoco  for the durat on of p anned part c pat on un ess the dev at ons put the subject at r sk or the 
subject’s cond t on requ res that he/she be d scont nued from the study. 
5.0 STUDY MATERIALS 
5.1 
DESCRIPTION OF TEST ARTICLE 
The HARMONI™ Modu ar Tor c Intraocu ar Lens (HMTIOL) System s des gned to a ow safe exchange or adjustment 
of an IOL opt c after mp antat on. 
 
 
 
 
 
  
 
 
 
. 
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5.1.1 INSTRUCT ONS FOR USE  
Refer to the Surg ca  Gu de for a  use and adm n strat on deta s. 
5.2 
PACKAGING AND LABELING 
A  packag ng and abe ng w  be cons stent w th the current study des gn. The abe ng w  nc ude at a m n mum, the 
fo ow ng: 
• 
Sponsor name and address 
• 
“For S ng e Use On y” statement (or equ va ent symbo ) 
• 
Ster ty symbo  
• 
Storage temperature range requ rements or equ va ent (e.g. “Store at room temperature.”) 
• 
Exp rat on date 
• 
Power des gnat on 
• 
Un que ser a  number 
• 
Mode  number 
5.3 
ACCOUNTABILITY 
The Invest gator s respons b e for keep ng accurate accountab ty records of the number of study enses rece ved, 
d spensed, and returned to Sponsor. The study enses must be stored under the appropr ate cond t ons n a secure 
area and are to be mp anted on y n subjects enro ed n the study, n accordance w th the cond t ons spec f ed n th s 
protoco .  
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A  accountab ty records w  nc ude the fo ow ng: 
• 
Mode  and ser a  numbers 
• 
Rece pt date 
• 
Quant t es rece ved 
• 
In t a s (attr butab ty) of s te personne  who rece ved, d spensed, or returned study enses 
• 
Date of use 
• 
Subject and eye treated w th the study ens (by Subject ID and In t a s on y) 
• 
Date returned to Sponsor 
• 
Defect ve or damaged study dev ces  
Per od ca y throughout the study and/or upon comp et on, the Sponsor (or des gnee) w  rev ew and ver fy the 
Invest gator’s accountab ty records. Fo ow ng ver f cat on, and as d rected by the Sponsor, a  unused and exp anted 
products must be returned to the Sponsor.  
Note: In addition, any study lenses or components deemed defective, damaged, malfunctioning, or explanted must be 
retained by the site and returned to the Sponsor for evaluation. Under no circumstances are any components to be 
discarded or otherwise disposed of. If there is any question as to the applicability of this directive, consult the Protocol 
Contacts page of this protocol and discuss the situation with a Sponsor representative.  
5.4  
OTHER MATERIALS 
Add t ona  mater a s can be prov ded to s tes for the durat on of the study on an as-needed bas s and may nc ude: 
• 
ETDRS ght box, g are source, and charts to perform the standard zed VA assessments descr bed n the Manua  
of Procedures 
• 
Med ce  njectors (for study ens nject on on y) 
• 
S t amp camera 
6.0 ADVERSE EVENTS 
Safety assessments nc ude adverse events/ser ous adverse events, and adverse dev ce events. The report ng t me 
per od s from the t me of consent through the ast study v s t (3 Month V s t post cataract extract on).  
6.1 
DEFINITIONS  
6.1.1 ADVERSE EVENT (AE) 
An AE s any untoward med ca  event n a subject that does not necessar y have a causa  re at onsh p to the 
study dev ce or protoco . AEs nc ude Adverse Dev ce Effects (ADEs). Cond t ons or d seases that are pre-
ex st ng and/or chron c but stab e shou d not be recorded on AE pages of the eCRF.  S m ar y, changes n a 
pre-ex st ng and/or chron c cond t on of d sease that are cons stent w th natura  d sease progress on are NOT 
adverse events and a so shou d not be recorded on the AE pages of the eCRF.   
Refer to Sect on 6.3.1 for nstruct ons regard ng events that requ re exped ted report ng to the Sponsor and 
IRB/EC. 
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Exper ence w th cataract surgery and the mp antat on of IOLs has shown that some cond t ons can be 
cons dered norma  or expected events fo ow ng these procedures. The fo ow ng may be cons dered norma  
or expected events after cataract surgery and on y need to be reported as AEs as spec f ed here: 
• 
Ir t s (ce  / f are) – f treated onger than standard post-operat ve reg men or f t recurred after comp ete 
reso ut on 
• 
Pers stent Cornea  Stroma Edema ( f present at 1 Month) 
• 
Increased IOP on y f med ca /surg ca  ntervent on s requ red ( .e. med cat on, paracentes s man pu at on) 
• 
BCDVA decrease of 10 or more etters (2 nes) from any prev ous v s t not secondary to any under y ng 
cond t on present at t me of enro ment 
• 
Any expected post-operat ve ocu ar event requ r ng a change n standard postoperat ve med cat on 
reg men 
Note: PCO is not to be reported as an AE, as per ISO 11979-7:2014.  
Note: The HMTIOL is designed for safety and ease of optic exchange and rotational adjustment post-primary 
cataract surgery. Optic exchange and optic rotation to refine refractive outcomes are not to be reported as 
AE’s. 
Part cu ar attent on shou d be pa d to ensure t me y and accurate report ng of any of the fo ow ng cataract 
surgery re ated events: 
• 
Endophtha m t s 
• 
Capsu ar njury 
• 
V treous oss 
• 
Macu ar edema 
• 
Ret na  detachment 
• 
Lens d s ocat on 
• 
Moderate to severe cornea  edema 
• 
Pup ary b ock / ang e c osure 
• 
Hypopyon or hyphema 
6.1.2 ADVERSE DEV CE EFFECT (ADE) 
An ADE s any untoward or un ntended effect, event, or response surround ng and w th a causa  re at onsh p 
w th the use of a med ca  dev ce. Th s def n t on may nc ude any event resu t ng from nsuff c enc es or 
nadequac es n the nstruct ons for use or the dep oyment of the dev ce or other dev ce ma funct ons. Th s 
def n t on nc udes any event that s a resu t of a user error and any event that affects a user of the dev ce ( .e. 
careg ver, bystander, etc.). 
6.1.3 UNANT C PATED ADVERSE DEV CE EFFECT (UADE) 
A UADE s any ADE, wh ch s unant c pated and poses a r sk to hea th or safety, or any fe-threaten ng prob em 
or death caused by or assoc ated w th a dev ce, f that effect, prob em, or death was not prev ous y dent f ed 
n nature, sever ty or degree of nc dence (see Invest gator Brochure [IB]). UADEs a so nc ude any 
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unant c pated s ght-threaten ng events and any other unant c pated ser ous prob em assoc ated w th a dev ce 
that re ates to the r ghts, safety, or we fare of subjects.  
6.1.4 DEV CE DEF C ENC ES (DD) 
A Dev ce Def c ency (DD) s a fa ure of the dev ce to meet ts performance spec f cat ons or expectat ons, or 
otherw se not perform as ntended. Th s can nc ude e ther a ma funct on or damage to the dev ce or any 
part thereof, regard ess of the source of ma funct on or damage, nc ud ng user error, and regard ess of the 
presence of njury (or ack thereof) to subject, user, or bystander.  
6.2 
AE EVALUATION  
AEs exper enced n th s study may be assoc ated w th the study dev ce ( .e. ADE) or the study protoco  as demonstrated 
n the fo ow ng non-exhaust ve st of examp es: 
Study Dev ce (ADE) 
• 
IOL d s ocat on 
• 
Exp ant due to hapt c break/damage 
• 
Exp ant due to base and/or opt c damage 
Study Protoco  
• 
A erg c react on to d at ng drops 
• 
Lens remnants fo ow ng surgery 
• 
Capsu ar tear dur ng surgery to mp ant study dev ce 
6.2.1 EVALUAT ON 
A  AEs w  be eva uated for and by the fo ow ng cr ter a: 
• 
C ass f cat on (SAE, AE, ADE or comb nat on) 
• 
D agnos s (or descr pt on f ADE) 
• 
Sever ty 
• 
Re at onsh p (Causa ty) to study protoco  or dev ce 
• 
Outcome 
• 
Treatment or act on taken 
 
6.2.1.1  
CLASSIFICATION 
When eva uat ng AEs, the Invest gator must determ ne f the event s ser ous us ng the fo ow ng gu de nes: 
A Serious Adverse Event (SAE) s any AE (ocu ar or non-ocu ar) that: 
• 
resu ts n death 
• 
resu ts n ser ous njury, def ned as: 
¨ 
fe-threaten ng  
¨ permanent mpa rment of a body funct on (e.g. b ndness) or structure  
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¨ necess tates med ca  or surg ca  ntervent on to prevent permanent mpa rment of a body funct on or 
permanent damage to a body structure, or 
¨ resu ts n a potent a y s ght-threaten ng cond t on 
• 
s a ma funct on that m ght cause or contr bute to a ser ous njury or death f t were to recur 
• 
requ res n-pat ent hosp ta zat on or pro ongat on of ex st ng hosp ta zat on*, or 
• 
eads to feta  d stress, feta  hea th, a congen ta  abnorma ty, or b rth defect  
* Hosp ta zat on s a cr ter on for assessment of ser ousness. Hosp ta zat on n the absence of a med ca  AE s 
not n tse f an AE. For examp e, the fo ow ng reports of hosp ta zat on w thout a med ca  AE shou d not be 
cons dered e ther ser ous or an AE:  
• 
adm ss on for treatment of a pre-ex st ng cond t on not assoc ated w th the deve opment of a new AE or 
w th worsen ng of the pre-ex st ng cond t on (e.g. for work-up of pers stent pretreatment ab abnorma ty)  
• 
soc a  adm ss on (e.g. subject has no p ace to s eep)  
• 
adm n strat ve adm ss on (e.g. for year y phys ca  exam)  
• 
opt ona  adm ss on not assoc ated w th a worsen ng of a pre-ex st ng cond t on (e.g. e ect ve cosmet c 
surgery or e ect ve surgery for pre-ex st ng repa r of the Ach es tendon [wh ch had not worsened wh e 
on study]) 
• 
hosp ta zat on for adm ss on w thout a med ca  AE 
NOTE: For the purposes of this protocol, any UADE will be considered an SAE.  
6.2.1.2  
DIAGNOSIS OR DESCRIPTION 
In a  nstances, t s preferab e to report a  AEs and SAEs by d agnos s rather than a s gn or symptom f poss b e. 
Th s may necess tate the rev s on of a prev ous y reported AE or SAE as more nformat on s obta ned.  
6.2.1.3  
SEVERITY 
When eva uat ng AEs, the Invest gator must determ ne the sever ty of symptoms us ng the fo ow ng 
gu de nes: 
• 
M d: Subject awareness of a s gn or symptom that s eas y to erated, requ res no treatment, and does 
not nterfere w th the subject’s da y act v t es 
• 
Moderate: Subject awareness of a s gn or symptom wh ch may be a ow eve  of concern to the subject 
and may nterfere w th da y act v t es, but can be re eved by s mp e therapeut c care 
• 
Severe: A s gn or symptom that nterrupts the subject’s da y act v ty and requ res system c therapy or 
other treatment 
6.2.1.4  
RELATIONSHIP (CAUSALITY) TO STUDY DEVICE OR STUDY PROTOCOL  
When eva uat ng AEs, the Invest gator must eva uate the re at onsh p of the event to the study dev ce and 
study protoco , us ng the fo ow ng gu de nes: 
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• 
Not Re ated: AEs wh ch are c ear y and ncontrovert b y due to causes other than the study dev ce or study 
protoco  (e.g. concom tant d sease, etc) 
• 
Re ated: AEs wh ch are fe t w th a reasonab e degree of certa nty to be re ated to the study dev ce or study 
protoco  
• 
Unknown: Adverse events for wh ch a connect on w th the study dev ce or study protoco  cannot be ru ed-
out w th certa nty, or not enough nformat on s ava ab e to assess the re at onsh p 
6.2.1.5  
OUTCOME 
The c n ca  outcome of an AE w  be categor zed as fo ows: 
• 
Reso ved w thout seque ae 
• 
Reso ved w th seque ae (spec fy) 
• 
Ongo ng ( .e. cont nu ng at t me of study d scont nuat on) 
• 
Death 
6.2.1.6  
TREATMENT OR ACTION TAKEN 
Treatment or Act on Taken w  be categor zed as fo ows: 
• 
None 
• 
Med ca  Intervent on (spec fy on Concom tant Med cat on Source and eCRF) 
• 
Surg ca  Intervent on (spec fy on Concom tant Procedure Source and eCRF) 
• 
Other (spec fy) 
6.3 
REPORTING 
6.3.1 ON-S TE EXPED TED REPORT NG 
The Invest gator s ob gated to report the fo ow ng to the Sponsor w th n 24 hours of becom ng aware of the 
event to ensure the safety of a  part c pants n the study and to meet regu atory report ng requ rements: 
• 
A  SAEs, regard ess of re at onsh p to study dev ce or study protoco  ut z ng the SAE/ADE Report Form 
• 
A  AEs determ ned to be re ated to the study dev ce (ADEs or UADEs) ut z ng the SAE/ADE Report Form 
• 
A  HMTIOL exp ants (consu t Med ca  Mon tor sted on Protoco  Contacts page pr or to exp ant, f 
poss b e) 
• 
A  Dev ce Def c enc es (DD) ut z ng the DD Report Form 
Refer to the Protocol Contacts page for appropriate Sponsor contact to report the above events. 
NOTE: Any explanted HMTIOL devices, exchanged HMTIOL optics, or any components of the HMTIOL System 
presenting a deficiency or malfunction are to be retained by the site until collected by the Sponsor. Under 
no circumstances are they to be destroyed or otherwise discarded. 
When report ng these events to the Sponsor, the s te shou d forward any support ng documents a ong w th 
the appropr ate report ng form and comp ete the correspond ng eCRF, f app cab e. S tes must a so report 
app cab e events to the rev ew ng IRB/EC per ts estab shed report ng procedures. 
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6.3.2 OFF-S TE SAE REPORT NG 
As a mu t center c n ca  tr a , the Invest gators may rece ve “off-s te” reports (e.g. an SAE Report). These are 
Sponsor reports of SAEs wh ch occurred at other s tes for the same tr a , or n d fferent tr a s us ng the same 
test art c e, that met the cr ter a for report ng. These shou d be reported to the rev ew ng IRB per the r 
estab shed report ng procedures. 
6.3.3 REPORT NG OF COMPLA NTS FOR ANC LLARY MARKETED PRODUCTS 
Any comp a nts, ma funct ons or s m ar events re ated to anc ary marketed products used n th s study 
shou d be reported by the Invest gators n accordance w th the reference nformat on prov ded on the 
assoc ated commerc a  packag ng.  
6.3.4 ADVERSE EVENTS AND SER OUS ADVERSE EVENTS AT SUBJECT EX T 
Ongo ng SAEs and ADEs w  be fo owed unt  reso ut on or no further change n the cond t on s expected. 
Non-ser ous AEs that are ongo ng at study ex t v s t or upon d scont nuat on from the study w  be fo owed 
per the Invest gator’s standard of care. Documentat on n the eCRF of th s fo ow-up s not requ red a though 
subject care shou d cont nue as appropr ate.  
6.4 
SAFETY MONITORING AND REVIEW 
A  reported AEs w  be rev ewed on a week y bas s and assessed for trend ng and causa ty to study dev ce or procedure  ADEs, 
UADEs, DDs, and SAEs w  be rev ewed upon rece pt of exped ted report ng (Sect on 6 3 1)  Any unexpected trends or events w  
necess tate carefu  rev ew and assessment of any change n the r sks assoc ated w th part c pat on or study cont nuat on   
f an event occurs affect ng a sub ect’s r sk of part c pat on, Off S te Report ng (Sect on 6 3 2) w  be ut zed to update s tes and 
the RB(s) / EC(s)  f the safety prof e of the event prov des for the cont nuat on of the study, nformed Consent Forms w  be 
rev sed as necessary to ensure sub ects’ consent to cont nue part c pat on g ven the known rev sed r sks  
As out ned n Sect on 4 7 1, the Sponsor reserves the r ght to d scont nue enro ment at any t me  
7.0  STUDY OUTCOMES 
7.1 
SAFETY OUTCOMES 
Safety w  be eva uated by assess ng the fo ow ng: 
• 
Preservat on of BCDVA  
• 
Rate of dev ce-re ated SSI’s other than opt c exchange and rotat ona  adjustment of the HMTIOL 
• 
AE rates  
• 
Dev ce def c enc es  
 
7.2 
PERFORMANCE OUTCOMES 
• 
Ca cu at on of Standard error of the mean n ens power A-constant for ref nement 
• 
1 and 3 months MRCYL for eyes mp anted w th HMTIOL 
• 
1 and 3 months MRCYL pred ct on error for eyes mp anted w th HMTIOL 
• 
1 and 3 months MRCYL pred ct on error for eyes mp anted w th HMTIOL per vector ana yses 
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• 
1 and 3 months SEQ pred ct on error 
• 
UCDVA by study v s t 
o Percent of eyes that ach eve  
§ 
20/20 or better 
§ 
20/25 or better 
§ 
20/32 or better 
§ 
20/40 or better 
§ 
Worse than 20/40 
• 
BCDVA by study v s t 
o Percent of eyes that ach eve  
§ 
20/20 or better 
§ 
20/25 or better 
§ 
20/32 or better 
§ 
20/40 or better 
§ 
Worse than 20/40 
• 
IOL mer d an m sa gnment on the day of surgery 
• 
Rotat ona  of IOL mer d an at 1 day, 1 week, 1 and 3 months  
o Percent of eyes w th rotat on £ 5  
o Percent of eyes w th rotat on < 10  
o Percent of eyes w th rotat on < 20  
o Percent of eyes w th rotat on < 30  
o Abso ute va ue of rotat on  
o 
  
• 
Reduct on n cy nder power of the eye mp anted w th HMTIOL (abso ute preoperat ve magn tude of cornea  
cy nder (K) m nus the abso ute postoperat ve magn tude of MRCYL at the cornea  p ane) 
• 
Percentage reduct on n cy ndr ca  power of the eye mp anted w th HMTIOL (abso ute preoperat ve 
magn tude of cornea  cy nder (K) m nus the abso ute postoperat ve magn tude of MRCYL at the cornea  
p ane, expressed as a percentage of the abso ute preoperat ve magn tude of tota  cornea  cy nder (K)). 
 
 
 
 
8.0 STATISTICAL METHODS  
Th s s a study to eva uate the safety and performance of HTMIOL n subjects undergo ng cataract surgery.  In genera , 
the ana yses w  be prov ded based on ava ab e data.  The mean, standard dev at on, m n mum, and max mum w  
be prepared for the cont nuous c n ca  parameters, and counts and percentages w  be presented for the categor ca  
outcomes.  
8.1 
SAMPLE SIZE CALCULATION 
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The samp e s ze of th s study s based on ref nement of A-constant ( ens power constant). To reduce b as due 
to surg ca  techn que, unusua  eyes and d fferences n equ pment (A scan, keratometer, etc.) data w  be 
obta ned from a suff c ent number of eyes such that the standard error of the mean n ens power constant s 
ess than ±0.10mm (approx mate y ±0.2D). A m n mum of 20 to 30 eyes from each surgeon shou d be 
adequate to ach eve the to erance. Each nc uded subject shou d have a post-operat ve uncorrected v sua  
acu ty better than 20/40 to avo d naccurac es n refract on. 
Th s s a feas b ty study and no hypothes s test ng w  be performed. 
8.2 
ANALYSES POPULATIONS 
Subjects that are screened but d squa f ed based on the preoperat ve and ntra-operat ve e g b ty cr ter a 
w  be exc uded from the safety and performance data ana yses.  However, the r reasons for the screen fa ure 
w  be summar zed.  The ana yses popu at ons are def ned be ow.   
8.2.1 SAFETY POPULAT ON 
The Safety Population nc udes eyes w th attempted study ens mp antat on, (successfu  or aborted after 
contact w th the eye). The ntraoperat ve and postoperat ve AEs and DDs w  be summar zed based on the 
safety popu at on.   
8.2.2 IMPLANTED-EYE POPULAT ON 
The Implanted-Eye Popu at on cons sts of eyes w th successfu  HMTIOL mp antat on. S nce t s mportant to 
eva uate HMTIOL’s effect on a  study eyes, s t amp exam nat on, ntraoperat ve pressure (IOP), and d ated 
fundus exam nat on (DFE) w  be based on the mp anted-eye popu at on.   
Add t ona y, the UCDVA, BCDVA, pred ct on error, and mer d an rotat on w  be eva uated based on the 
mp anted-eye popu at on. 
8.2.3 PER PROTOCOL POPULAT ON 
The Per Protocol (PP) Popu at on conta ns eyes w th successfu  HMTIOL mp antat ons dur ng surger es and 
do not have a major protoco  dev at on (such as mproper y enro ed n the study or ens power ca cu at on 
errors) and w  be cons dered the pr mary popu at on for the ana ys s of performance outcomes.  The 
performance outcomes (UCDVA, BCDVA, and pred ct on error) w  a so be eva uated based on the per 
protoco  popu at on. 
The protoco  dev at ons w  be categor zed pr or to the ana ys s. 
 
 
 
 
 
 
 
 
 
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8.3 
STATISTICAL METHODS 
The data ana yses w  be based on the ana ys s popu at ons descr bed above.  No mputat on for m ss ng data 
w  be performed.  The demograph c data w  be summar zed based on study subjects.  
For cont nuous outcomes, mean, standard dev at on, med an, m n mum, and max mum w  be prov ded.  For 
categor ca  outcomes, the counts and percentages of eyes w th each categor ca  eve  of outcomes w  be 
summar zed. 
8.3.1 SAFETY OUTCOMES 
8.3.1.1  
ADVERSE EVENTS AND DEVICE DEFICIENCIES 
Adverse events and dev ce def c enc es w  be summar zed at each study v s t based on the safety popu at on.  
The number and percentage of eyes reported w th the 3-month cumu at ve and pers stent adverse events w  
be ca cu ated. 
 
 
  
 
 
   
8.3.2 PERFORMANCE OUTCOMES 
The performance outcomes w  be ana yzed based on the Imp anted-eye Popu at on and PP Popu at on.  The 
BCDVA w  a so be summar zed based on the Best-case popu at on as suggested by ISO.  
8.3.2.1  
BCDVA 
 
 
   
 the number and percentage of eyes reach ng BCDVA 20/20 or better, 20/25 or better, 20/32 or 
better, 20/40 or better, and worse than 20/40 at each v s t w  be prepared.  
 
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8.3.2.2  
UCDVA 
The proport on of eyes w th UCDVA of 20/20 or better, 20/25 or 
better, 20/32 or better, 20/40 or better, and worse than 20/40 at each v s t w  be summar zed at the pre-
operat ve and every postoperat ve v s ts.   
8.3.2.3  
PREDICTION ERROR (PE) 
The MRSE pred ct on error w  be ca cu ated at 3 months for each mp anted eye as fo ows: 
MRSE PE = Postoperative MRSE adjusted to 6 meters – MRSE TRRE (target residual refractive error) 
The MRCYL pred ct on error w  be ca cu ated at 3 months for eyes mp anted w th HMTIOL as fo ows: 
MRCYL PE = Postoperative MRCYL adjusted to 6 meters – MRCYL TRRE (target residual refractive error) 
The MRCYL PE w  a so be ca cu ated based on the vector ana ys s approach for eyes mp anted w th the 
HMTIOL. 
 
 
 
 
   
8.3.2.4  
MISALIGNMENT OF IOL MERIDIAN 
The f na  rotat ona  mer d an of the IOL w  be compared to the p anned pos t on. The abso ute va ue of 
rotat on w  be descr bed by mean, med an, and max mum va ues. 
 
  
 
8.3.2.5  
ROTATION OF IOL MERIDIAN 
The rotat on of IOL mer d an w  be ca cu ated for each eye from Day 0 to every postoperat ve v s t.  The 
descr pt ve stat st cs for cont nuous var ab es w  be used to summar ze the rotat on ang e at each v s t. The 
abso ute va ue of rotat on w  be descr bed by mean, med an, and max mum va ues. 
 
The number and percentage of eyes 
w th rotat on £ 5 , < 10 , < 20 , and < 30  w  be ca cu ated at each v s t.    
 
8.3.2.6 
REDUCTION IN CYLINDER POWER 
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The reduct on n cy nder power w  be ca cu ated for each eye mp anted w th the HMTIOL as fo ows: 
Cylinder Power Reduction = absolute value of preoperative magnitude of corneal cylinder (K) – 
absolute postoperative magnitude of MRCYL at the corneal plane. 
The percent reduct on n cy ndr ca  power w  be ca cu ated for eyes w th non-zero preoperat ve cornea  
cy nder as fo ows: 
Cylinder Power % Reduction = Cylinder Power Reduction/ absolute value of preoperative magnitude of 
corneal cylinder (K) × 100. 
The descr pt ve stat st cs for cont nuous var ab es w  be used to summar ze these outcomes at each v s t.  
 
 
 
  
The vector ana yses (Eyde man11) based on the cy nder power and ax s w  be performed. 
 
   
9.0 DATA MANAGEMENT 
9.1 
DATA QUALITY ASSURANCE 
A  requested nformat on must be entered on the eCRF and conf rmab e through source documentat on. If an tem s 
not ava ab e or not app cab e, th s fact shou d be c ear y nd cated. 
Data w  be entered nto a computer database deve oped spec f ca y for th s tr a . Dur ng the course of the tr a , 
quer es w  be generated for data po nts that are potent a y erroneous and requ re appropr ate c ar f cat on or 
correct on. 
9.1.1 DATA MON TOR NG 
Per od c mon tor ng (e ther remote and/or on-s te) w  take p ace to ensure data ntegr ty. Study mon tor ng 
nvo ves the fo ow ng e ements: 
C arV sta personne , or des gnee, may meet w th nvest gators pr or to the n t at on of the study n order to 
rev ew the adequacy of the subject popu at on, fac t es, and equ pment w th respect to the needs of the 
study, and to fam ar ze the nvest gator and support staff w th the study protoco . 
C arV sta personne , or des gnee, may meet w th the nvest gators at the t me enro ment s n t ated n order 
to ensure that subjects are be ng proper y se ected, that the methods descr bed n the study protoco  are 
thorough y understood by the nvest gator, and that study data are be ng correct y recorded. 
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C arV sta personne , or des gnee, may v s t the c n ca  s te at any t me dur ng the course of the study to rev ew 
and/or co ect comp eted case report forms. Add t ona y, te ephone consu tat on w  occur as necessary 
dur ng the course of the study to ensure the proper progress and documentat on of the study f nd ngs. 
The study data w  be carefu y protected, and mask ng ut zed to the extent poss b e, n order to prevent 
b as.  
9.2 
RECORD RETENTION 
The nvest gator sha  ma nta n a  subject records for wh chever of the fo ow ng per ods s shorter: 
• 
A per od of two years after the date on wh ch FDA approves the market ng of the dev ce  
• 
A per od of f ve years after the date on wh ch the resu ts of the study are subm tted to the FDA n support of 
the market ng of the dev ce  
OR 
• 
A per od equa  to the m n mum requ red by the reg ona  author ty. 
The Invest gator / S te must contact C arV sta as prov ded n the Protoco  Contacts page pr or to d scard ng or 
d spos ng of any study re ated supp es or documents. The Sponsor reta ns the r ght to have a  study documents 
sh pped (at Sponsor’s expense) for arch va  purposes, as an a ternat ve to d sposa . 
 
10.0 REFERENCES 
1. Joshua D. Ste n, MD. Ser ous adverse events after cataract surgery. Current Opinions in Ophthalmology 23 2012 
May: 219-225. 
2. Sverker Norrby, PhD. Sources of error n ntraocu ar ens power ca cu at on. Journal of Cataract and Refractive 
Surgery 34 2008 Mar: 368-376 
3. Retz aff JA, Sanders DR, Kraff MC. Deve opment of the SRK/T ntraocu ar ens mp ant power ca cu at on formu a. 
J Cataract Refrat Surg 1990 May: 16; 333-340 
4. L m LH, Lee SY, Ang CL. Factors affect ng the pred ctab ty of SRK II I pat ents w th norma  ax a  ength 
undergo ng phacoemu s f cat on surgery. Singapore Med J 2009; 50 (2) 120-125 
5. Ga e RP, Sa dana M, Johnston RL et a . Benchmark standards for refract ve outcomes after NHS cataract surgery. 
Eye 23, no. 1 2009 Jan: 149-152. 
6. Ar st odemou P, Cartwr ght NE, Sparrow JM, Johnston RL. Intraocu ar ens formu a constant opt m zat on and 
part a  coherence nterferometry b ometry: refract ve outcomes n 8108 eyes after cataract surgery. J Cataract 
Refract Surg 2011; 37:50 – 62. 
7. Evans, BJW. Monov s on: a rev ew. Ophthal. Physiol. Opt. 2007; 27: 417-439 
8. Er ckson, D.B. & Er ckson, P. Psycho og ca  factors and gender d fferences n the acceptance of 
monov s on. Perceptual and Motor Skills, 2000; 91:1113-1119. 
9. Back AP, Ho den BA, H ne NA. Correct on of presbyop a w th contact enses: comparat ve success rates w th 
three systems. Optometry & Visual Science. 1989 Aug; 66(8): 528-25  
10. Du To t R, Ferre ra, JT, Ne  ZJ. V sua  and Nonv sua  Var ab es Imp cated n Monov s on Wear. Optometry & 
Visual Science. 1998; 75 (2): 119-125 
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11. Eyde man M, et a . Standard zed Ana yses of Correct on of Ast gmat sm by Laser Systems That Reshape the 
Cornea. J of Refract ve Surg. 2006; 22: 81-95. 
 
 
 
 
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