J. Colin, MDASCRS 2008

Visual and Safety Performance of the AcrySof® Phakic IOL in Global Clinical Trials

Prof. Joseph Colin, MDChef du Service d'Ophtalmologie - CHU PellegrinBordeaux, France(Financial Disclosure: Consultant, Alcon)

EU Phase 3 Clinical Investigators

•J. Alió, MD (Alicante, Spain)•J.L. Arné, MD (Toulouse, France)•R. Bellucci, MD (Verona, Italy)•B. Cochener MD (Brest, France)•J. Colin, MD (Bordeaux, France)•R.H. Gerl, MD (Ahaus, Germany)•M. Knorz, MD (Mannheim, Germany)•T. Kohnen, MD (Frankfurt, Germany)•A. Marinho, MD/F. Vaz, MD (Porto, Portugal)

Canada Phase 3 Clinical Investigators• T. Demong, MD (Calgary, Alberta)• S. Holland, MD (Vancouver, British Columbia)• M. Pop, MD (Montreal, Quebec)• T. Rabinovitch, MD (Downsview, Ontario)• F. Roy, MD (Trois-Rivieres, Quebec)

US Phase 2 Clinical InvestigatorsJ. D. Horn, MD (Nashville, Tennessee )R. Krueger, MD (Cleveland, Ohio)S. S. Lane, MD (Stillwater, Minnesota)W. A. Maxwell, MD, PhD (Fresno, California)K. Solomon, MD (Charleston, South Carolina)

J. Colin, MDASCRS 2008

Clinical Study Design

Clinical Objective: Investigate safety & effectiveness Study design: Non-randomized, open label, single arm,

multicenter clinical investigations Pooled analysis of global clinical studies

360 subjects included in total analysis European Phase 3 Clinical Study: 190 subjects Canadian Phase 3 Clinical Study: 120 subjects US Phase 2 Clinical Study: 50 subjects

3 to 5 year follow-up duration Results reported for 2 year follow-up visit (n=204)

Optic 6.0 mm

Overall length 12.5 mm

to 14.0 mm

Diopter Range -6.0 D to -16.5 D

L-Series AcrySof® PIOL

Not approved for general use.

Anterior Chamber Angle-Supported Single-Piece IOL design Soft Acrylic (AcrySof® IOL

material) Monarch® II IOL Delivery

System Small incision size

J. Colin, MDASCRS 2008

Study Criteria

Main Inclusion Criteria Adults >18 years of age, with cap of 49 years of age

for US and Canadian study Stable, moderate to high myopia (refraction within ±0.5

D at least 12 months prior to surgery) Able & willing to sign informed consent

Main Exclusion Criteria Previous ocular surgery Glaucoma or family history of glaucoma Mesopic pupil size >7.0 mm Astigmatism >2.0 D Anterior chamber depth <3.2 mm Non-qualifying endothelial cell density per age criteria

J. Colin, MDASCRS 2008

Postoperative Evaluation

Endothelial Cell Density (ECD) & Morphology Adverse Events (AE) Maintenance of Best Spectacle-Corrected

Visual Acuity (BSCVA) Uncorrected Distance Visual Acuity (UCVA) Best Spectacle-Corrected Distance Visual

Acuity (BSCVA) Manifest Refraction Spherical Equivalent

(MRSE) Predictability of Refraction

Endothelial Cell Density

Mean Chronic % Change in ECD (Annualized)

2 years postop (from 6 months postop)

Mean Acute % Change in ECD(Actual)

6 months postop (from preop)

Minimal effects on Acute & Chronic ECD

-3.31 -2.98

-10-8-6-4-202468

10

Central, n=348 Peripheral, n=342

Me

an

EC

D %

Ch

an

ge

0.04

-0.31

-6

-4

-2

0

2

4

6

Central, n=197 Peripheral, n=191

Mea

n %

EC

D C

han

ge

Endothelial CellPercent Hexagonality

Preop vs. 2 year visit

Endothelial CellCoefficient of Variation

Preop vs. 2 year visit

Stable Cell Morphology@ 2 year visit

Endothelial Cell Morphology

57.70 57.8257.57

57.97

0

10

20

30

40

50

60

70

Central Peripheral

Mea

n %

Hex

ago

nal

ity

Preop 2 year

33.20 33.5332.26 32.03

0

10

20

30

40

Central Peripheral

Mea

n C

ell C

oeff

icie

nt o

f Var

iatio

nPreop 2 year

Cystoid Macular Edema 0 0%

Corneal Stromal Edema 0 0%

Corneal Haze 1 0.3%

Hyphema 0 0%

Hypopyon 0 0%

Intraocular Infection /Endophthalmitis 0 0%

Lens Dislocation 0 0%

Pupillary Block 0 0%

Retinal Detachment / Repair 0 0%

Raised IOP Requiring Treatment @ ≥1 month(Raised IOP Requiring Tx occurring @ ≥1 month due to:

Steroid Responders [8], Surgical Procedure [1], & Unknown Etiology [1].

One subject experienced 2 incidences.

No persistent or ongoing cases at 2 year vist.)

10 2.8%

Cataract Formation (Related to: Surgical procedure [3], & Concurrent ophthalmic disease [2])

5 1.4%

Adverse EventsCumulative through 2 years postoperative

Out of 360Subjects

AE Description RateIncidence

Synechia (Goniosynechia) 6 1.7%

Pupil Ovalization 0 0%

Hospitalization for Raised IOP (On Operative Day) 5 1.4%

Secondary Surgical Intervention (SSI)**One subject experienced 2 incidences

9 2.5%

IOL Replacement (Power exchange [2])

New Suturing (1)

Prophylactic Treatment by Argon Laser (1)

Preventive Iridotomy (1)

Laser coagulation of retinal hole (1)

IOL Removal (4)

(Upside down placement [1], Patient dissatisfaction [2], Glare with

7.0 mm mesopic pupil size [1])

Adverse Events, cont’d.AE Description RateIncidence

Out of 360Subjects

J. Colin, MDASCRS 2008

Maintenance of BSCVA2 year visit

0 0 0

42.6

35.6

4.5

17.3

0

10

20

30

40

50

60

>2 LineDecrease

2 LineDecrease

1 LineDecrease

NoChange

1 LineIncrease

2 LineIncrease

>2 LineIncrease

% o

f S

ub

ject

s

N=202

0 0 0

42.6

35.6

4.5

17.3

0

10

20

30

40

50

60

>2 LineDecrease

2 LineDecrease

1 LineDecrease

NoChange

1 LineIncrease

2 LineIncrease

>2 LineIncrease

% o

f S

ub

ject

s

N=202

UCVA2 year visit

BSCVA2 year visit

0

10099.098.0

88.6

0

20

40

60

80

100

20/20 orbetter

20/25 orbetter

20/30 orbetter

20/40 orbetter

worse than20/40

% o

f S

ub

jects

N=202

0

10099.098.0

88.6

0

20

40

60

80

100

20/20 orbetter

20/25 orbetter

20/30 orbetter

20/40 orbetter

worse than20/40

% o

f S

ub

jects

N=202

2.5

97.593.5

80.5

65.0

0

20

40

60

80

100

20/20 orbetter

20/25 orbetter

20/30 orbetter

20/40 orbetter

worse than20/40

% o

f S

ub

jects

N=200

2.5

97.593.5

80.5

65.0

0

20

40

60

80

100

20/20 orbetter

20/25 orbetter

20/30 orbetter

20/40 orbetter

worse than20/40

% o

f S

ub

jects

N=200

Predictability of Refraction2 years postop

n=199

Mean Spherical

EquivalentPreop to 2 year

-10.41

-0.25 -0.22 -0.23 -0.25 -0.23

-12

-10

-8

-6

-4

-2

0

2

Preop,n=360

1 month,n=359

3 month,n=358

6 month,n=355

1 year,n=334

2 year,n=199

Mea

n S

ph

eric

al E

qu

ival

ent

(D

iop

ter)

78.4

94.0

0

20

40

60

80

100

within ± 0.5 D within ± 1.0 D

% o

f S

ub

jects

J. Colin, MDASCRS 2008

Conclusions: 2 year follow-up visit

Safety Outcomes Minimal effects on ECD at 2 years postop BSCVA maintained No chronic inflammation or persistently raised IOP Low rate of adverse events observed

Effectiveness Outcomes Excellent visual acuity High rate of predictability Refraction stable over time

Clinical investigations ongoing