Dimitri A Chernyak, PhDDirector of Research, AMO Inc.

February 24, 2007

Laser Corneal Refractive Surgeryto Correct Presbyopia

Laser Corneal Refractive Surgeryto Correct Presbyopia

The problem of Presbyopia

• Age-related loss of accommodation– Lose near visual acuity– 20s: Loss starts– Early 40s: Functional vision affected– Over 50: 100% of population presbyopic

• Conflicting theories– Hardening of lens/capsule (accepted)– Continual lens growth (disputed)– Weakening of ciliary muscle (unclear)

What can we do?• Corrections

– Glasses (Bi-, Trifocals, Progressives)– Contact lenses (multifocal/monovision)

• Ocular surface surgical procedures– Corneal procedures (change optics)

• Conductive Keratoplasty• Corneal ablation

– Monovision ablations– Multifocal ablations

– Scleral procedures (improve accommodation)• Laser Presbyopia Reversal (Surgilight)• Scleral expansion implants

• Intra-ocular procedures– Lens Exchange

• Multifocal IOLs• Accommodating IOLs

Inva

sive

nes

s

Outline of the Presentation

• Incidence and prevalence of Presbyopia• Clinical objectives for each indication• LVC scientific approaches to treatment of Presbyopia• Results to date• Issues and concerns• Ongoing research activities

Myopia23%

Hyperopia4%

Presbyopia14%

Myo + Presby5%

Hyper + Presby12%

No Correction42%

Vision Correction – World Wide Prevalence

Market Scope data

Outline of the Presentation

• Incidence and prevalence of Presbyopia• Clinical objectives for each indication• LVC scientific approaches to treatment of Presbyopia• Results to date• Issues and concerns• Ongoing research activities

Medicine bottle’s fine print20/300.15 logMAR

J1+4 638 EeaHXO

Map’s street names20/400.30 logMAR

J15 638 EeaHXO

Wall Street J. stock & fineprintMedicine bottle textPhone book

20//550.45logMAR

J36 638 EeaHXO

Wall Street Journal text20/700.55logMAR

J58 638 EeaHXO

Wall Street Journal Subtitles20/900.66 logMAR

J710 638 EeaHXO

20/1250.80 logMAR

J1014 638 EeaHXO

Real lifereading materials

Visual angleif hold print at 40cm

RosenbaumJaeger

Actual print size(MS Word-Arial)

*J2 is omitted since it is only 4% larger than J1 (20/41 instead of 20/40)

Clinical Objectives

• Original Goal: 20/25or betteruncorrected monoculardistance visionAND simultaneouslyJ3 or better uncorrectedmonocular near vision(“the box”)

• Myopia Patients may not be satisfied with 20/25distance vision. 20/20 & J3 might be more appropriatetarget

Unco

rrec

ted N

ear

Vis

ual

Acu

ity

Uncorrected Distance Visual Acuity

20/10 20/20 20/32 20/50 20/80 20/125

J2

J4

J6

J8

J10

J1+

Clinical Objectives

• Safety– BCDVA less then 2 lines loss

– No debilitating visual complaints

– Normal range of contrast sensitivity for the age group

• Efficacy– Good simultaneous near & distance visual acuity (the “box”)

– Subjective satisfaction with quality of vision

– Reduced or eliminated spectacle dependence

Outline of the Presentation

• Incidence and prevalence of Presbyopia• Clinical objectives for each indication• LVC scientific approaches to treatment of Presbyopia• Results to date• Issues and concerns• Ongoing research activities• Competition and IP

LVC Approach: Multifocality• Inadvertent induction of multifocality

– Early hyperopic treatments– Hyperopic/myopic treatment, overcorrection, opposite retreatment

• Mimicking glasses/contacts on the eye

• Systematic Research– Building a theoretical eye model– Determining an optimal shape for long depth of field– Simulating optical performance– Transferring theoretical model into real world

• Modify optics for long depth of focusDistance

Multifocal

Monofocal

Near

What is “Multifocality”?

The paths of light through the eye

Theory and practice

PreOp PostOp

Research Methodology• Optical modeling

– Using theoretical eye model determine pupil dynamics effects– Determining an optimal shape for long depth of field*– Simulating optical performance– Transferring theoretical model into real world

• PreVue lens studies• AO research in collaboration with Murcia University• Clinical Studies

– Intended vs. Achieved (Topography, wavefront, acuity,depth of focus, contrast)

– Patient satisfaction

*G. Dai, “Optical surface optimization for correction of presbyopia”, Applied Optics, Vol. 45 No. 17, 10 June 2006.

Simulated outcomes: Without correction

Distance Intermediate Near

Simulated outcomes: With correction

Distance Intermediate Near

PreVue Lens Study: Design Motivation

• Difficult to separate possible sources of “error”:– Design

– Treatment

– Biomechanical effects and healing

– Cortical effects (learning)

• Scleral shells (large contact lenses) for testing ofablation profiles without healing or learning effects

• Reusable subjects!!!

Visual Performance Evaluation

• Wavefront measurement• Pupil dynamics• Distance Visual Acuities (logMAR)

– High contrast (photopic & mesopic)– Low contrast

• Near Visual Performance

• Contrast performance– Low contrast Visual Acuities (logMAR)– Sine wave contrast sensitivity (logCS)– Small letter contrast sensitivity (logCS)

Binocular performance– Stereopsis– Worth 4 dot

• Subjective feedback– 30 mins near tasks– Binocular questionnaire

• Scale from 0 (perfect) to 10 (totally unacceptable)• Visual performance

(distance, intermediate, near, multi-tasking etc)• Visual symptoms

(ghost image, glare, halo etc.)• Satisfaction

Depth of Field (XY OD)

-0.20

0.00

0.20

0.40

0.60

0.80

1.00

4.00 3.00 2.50 2.00 1.50 1.00

Accom. Demand (D)

DC

NV

A (l

ogM

AR

)

Base line

R

B

H2

T

G1.3

Outline of the Presentation

• Incidence and prevalence of Presbyopia• Clinical objectives for each indication• LVC scientific approaches to treatment of Presbyopia• Results to date• Issues and concerns• Ongoing research activities

WaveScan Confirmation of Multifocality

Hyperopic Presbyopia(Pre-op)

Multifocal(Post-op)

-0.10

0.10

0.30

0.50

0.70

0.90

1.10

1.30

-0.20 -0.10 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90

Pre-op (n=16 Subjects)12 M (n= 16 Subjects)

20/25 or better

J3 o

r bet

ter

100% achieve 20/25 distance and J3 near 88% achieve 20/25 and J1

Hyperopic Presbyopia Clinical TrialUncorrected Distance and Near Vision at 12 Months with Bilateral Multifocal Eyes

Canadian Study: 82 eyes, 4 sites, 47 to 68 yrs, S: +0.5 3.5D, C: 0.0 1.5D

Hyperopic Presbyopia Clinical TrialUS Clinical Study Status

• Multifocal Non-Dominant Eye

• Database locked, case reports received

• Outcomes similar to Canadian study

• Expand US study to binocular multifocal treatments

• Remove contact lens portion of the US study

Uncorrected Distance Vision

0

65

0

95

55

100

0102030405060708090

100

% Eyes

20/20 or better 20/25 or better 20/40 or better

Monocular Uncorrected Distance Visionin Multifocal Eyes

(n=20)

Pre-Op

6 Months

0

70

0

95

70

100

0102030405060708090

100

% Eyes

20/20 or better 20/25 or better 20/40 or better

Monocular Uncorrected Distance Visionin Monofocal Eyes

(n=20)

Pre-Op

6 Months

0

100

20

100

80

100

0102030405060708090

100

% Subjects

20/20 or better 20/25 or better 20/40 or better

Binocular Uncorrected Distance Vision(n=20)

Pre-Op

6 Months

Satisfaction with Distance Vision

58

70

11 10

32

20

0

20

40

60

80

100

% Subjects

Satisfied/VerySatisfied

Not Sure Somewhat/VeryDissatisfied

Questionnaire Results for Both Eyes at Distance

Pre-Op (w/ correction)

6M (w/o correction)

Satisfaction with Near Vision

6065

2015

20 20

0

20

40

60

80

100

% Subjects

Satisfied/VerySatisfied

Not Sure Somewhat/VeryDissatisfied

Questionnaire Results for Both Eyes at Near

Pre-Op (w/ correction)

6M (w/o correction)

Uncorrected Distance and Near Vision at 6 Months in Monofocal Eyes

(n=20 Eyes)

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

1.2

-0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8

UCVA

UC

NVA Pre-Op

6 Months

70% (14/20) eyes are J3 or better50% eyes are J1 or better

Uncorrected Distance and Near Vision at 6 Months in Multifocal Eyes

(n=20 Eyes)

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

1.2

-0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6

UCVA

UC

NVA Pre-Op

6 Months

95% (19/20) eyes are J3 or better90% eyes are J1 or better

Binocular Uncorrected Distance and Near Vision at 6 Months

(n=20 Subjects)

-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

-0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6

UCVA

UC

NVA Pre-Op

6 Months

100% of patients at 6M are 20/20 J3.

Binocular Best Corrected Distance and Distance Corrected Near Vision at 6 Months

(n=20 Eyes)

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

-0.25 -0.2 -0.15 -0.1 -0.05 0 0.05 0.1

BSCVA

DC

NVA Pre-Op

6 Months

100% of patients at 6M are 20/20 J3.95% are 20/20 and J1

Outline of the Presentation

• Incidence and prevalence of Presbyopia• Clinical objectives for each indication• LVC scientific approaches to treatment of Presbyopia• Results to date• Issues and concerns• Ongoing research activities• Competition and IP

Current issues

• Research– Access to Adaptive Optics technology for testing shapes

• Commercial use (outside of USA)– Patient selection criteria

– Managing expectations

– Slower than regular CustomVue visual recovery

– Monocular vs. binocular treatments

• Other indications– Myopes and emmetropes have higher visual

demands than hyperopes

Outline of the Presentation

• Incidence and prevalence of Presbyopia• Clinical objectives for each indication• LVC scientific approaches to treatment of Presbyopia• Results to date• Issues and concerns• Ongoing research activities

Ongoing Research Activities

• Refinements in shape design based onOptical modeling, Clinical trials, and AdaptiveOptics experiments

• Research into combination treatmentmodalities IOL+LVC for monofocal and multi-focal IOLs

Questions/Comments?