Julie Kornfield, Bob Grubbs

Division of Chemistry & Chemical Engineering, Caltech

Sculpting Implants in situ: Light-Adjustable Intraocular Lens

Jagdish Jethmalani & Chris Sandstedt

Calhoun Vision

Robert Grubbs

Chemistry, Caltech

Dan Schwartz

Ophthalmology,

UCSF

Motivation

The Problem: Imperfections in wound healing and lens positioning create refractive errors (farsightedness, nearsightedness and astigmatism).

Retina Cornea

Lens

Pupil

Sclera

• Cataract Treatment:– extraction– replacement with an

intraocular lens (IOL)

• 14 million implants/yr. worldwide

• Current IOLs:

Clinical Need

• Cataract surgery is the most commonly performed surgery in patients over 65

• 50% of patients require spectacles afterward

Defocus, Lateral Displacement, Post-Operative Astigmatism (Unpredictable Wound Healing), Rotation.

• 98% of these are within ± 2 D.

• Cataract surgery is the most commonly performed surgery in patients over 65

• 50% of patients require spectacles afterward

Defocus, Lateral Displacement, Post-Operative Astigmatism (Unpredictable Wound Healing), Rotation.

• 98% of these are within ± 2 D.

Matrix[High mol. wt. poly(siloxane)]

Macromer[Low mol. wt. poly(siloxane)]

Photopolymerizable end groups

Photoinitiator(Light sensitive)

Design Principles for New Polymers

-Low glass transition temperature (-125 C)-Relatively rapid diffusionability to modify shape on large length scale

-Non-volatile -Insoluble in water

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>

Spatially resolved irradiation

h"locking"

h

Light-induced changes in shape and refractive index

Irradiation profile controlled by:- Transmission mask,- Spatial light modulator, or- Rastered laser

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- Once the desired shape is achieved, blanket irradiation makes it permanent

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QuickTime™ and aMotion JPEG B decompressor

are needed to see this picture.

Simple Characterization of Lenses

Ronchi Ruling

CCD Camera

TestSample

100 µmpinhole

300 Lines/inch

f=40 mmf=125 mm

He:Ne Laser

• Optical Quality• Controllable Shape Changes• Effective Photolocking• Permanent Shape After “Locking”• Prior to Adjustment, not altered by Ambient Light

Example of Power Change

Irradiate 2 min with 2 mW/cm2 at 325nm, allow 3 hr for diffusion:

Focal length reduced from 11mm to 4mm!

Ronchi InterferogramBefore Irradiation:

Lens quality matches current IOLs

Ronchi Interferogram After Irradiation

time post irradiation (hours)

-1.50

-1.00

-0.50

0.00

0 20 40 60

D

iop

ters

• 12 hours after adjustment is performed, the desired lens power is achieved.• 48 hours after adjustment is performed, irradiation of the entire lens makes

it permanent.

Adjustments occur Overnight

Experiments performed at Calhoun Vision.

Two weeks after surgery and irradiation, the eye is “quiet”.

Explanted lens for evaluation.

Biocompatibility of Material & Irradiation: in vivo evaluation in rabbit

Calhoun Vision and Dr. Nick Mamalis at the University of Utah, Salt Lake City, Utah

Dose-response relationship measured in the lab holds in vivo, too.

Animal-to-animal variability is small.

Adjustments in vivo are Precise and Predictable

Calhoun Vision and Dr. Nick Mamalis at the University of Utah, Salt Lake City, Utah

Precise Myopic, Hyperopic & Astigmatic Adjustments

Dose-Response Experiments performed at Calhoun Vision.

Increase

lens power

Decrease

lens power

Astigmatic

adjustment

Control orientation & magnitude.

Digital Light Delivery System

Designed & Manufactured with Carl Zeiss Meditec AG

Standard Slit-Lamp Footprint

User Friendly Software Texas Instruments Digital

Micromirror Device Unlimited Flexibility for

Lens Modifications

Clinical Implementation

Developed by Zeiss Meditec and Calhoun Vision.

Digital Mirror Device Projects Any Desired Intensity Profile

To decrease lens power To Increase lens power To correct astigmatism

It works in rabbits, but does it work in people?

•Initial clinical experiments (on blind eyes) did not give the predicted adjustment.

•Why?•Literature on the human cornea was inadequate:

–Transmission values from 30% to 75% were reported

–No information on lateral variations in transmission

•Careful experiments on human donor corneas: –Transmission values from 56% to 58% were found

–Attenuation is greater near the perimeter

Precise, predictable adjustments are achieved in patients.

0.00

0.25

0.50

0.75

1.00

1.25

1.50

1.75

2.00

2.25

AC01 AC05 AC06 AC07 AC09 AC12 AC13 AC22 AC23 AC34 AC38 AC44 AC48 AC49 AC53 AC54 AC56 AC57 JG01 JG03 JG04

Patient

Power Change

Target

Achieved

Results in Clinical Trials

Arbitrary Wavefront Correction

• Greyscale image of a tetrafoil fourth-order Zernike correction, projected on a LAL using a digital mirror device

• 3-D rendering of the Fizeau interference fringes of the LAL 24 hrs after irradiation with the tetrafoil spatial intensity profile.

C. Sandstedt (Calhoun Vision)

From the Eye Sight website of student Kyle Keenan at Steton Hall University.

Restoring Distance & Near Vision

Strategies for “Built-in Bifocals”

Multizone lens Diffractive lens on a Refractive lens

Irradiate to Add Multiple Zones

1.9 mm central region0.5 mm ring +2.3 D

1.8 mm central region0.6 mm ring +2.8 D

2.0 mm central region -2.5 D and 0.6 mm ring +2.8 D

Alternating Zones of ± 2 D

Experiments performed at Calhoun Vision.

Wavefront Image

Irra

dian

ce P

rofi

le

Phase Contrast Microscope Image

Irradiate to Add a Diffractive Lens

USAF Target ImagesCalhoun Vision Diffractive LAL +3.2 D Add

Distance Focus G4 E3 Near Focus G4 E1

Alcon ReStor IOL (SN#: 893599.049) +3.5 D Add

Distance Focus G4 E3 Near Focus G4 E2

Irradiation Patterns

Cylinder Tetrafoil

• Non-linear Response = Complicated Profiles• Currently empirical

Need for a theoretical model for systematic design.

Predicting Shape Change:Is this a previously solved problem?

• Well known:– Polymerization reaction kinetics– Diffusion processes in non-deforming media– Solid deformation caused by external forces

• Not so well known:– Deformation driven by diffusion

Some Interesting Features

• Deformation without external force– Mechanical loading is determined completely within

the object– The “load” is imposed by spatially-resolved chemical

reaction– Free surface boundary condition

• No material enters or leaves– Deformation arises from redistribution of material

within the object

Diffusion and Deformation in Polymeric Gels

• Stress-Diffusion Coupling Model (SDCM)– T. Yamaue and M. Doi (2004)– Restricted to situations in which an externally applied load on a rigid bounding

surface drives fluid out of the gel

• Mixture Theory approach– J. Shi, K. R. Rajagopal, and A. Wineman (1981)– Externally imposed pressure-drop across the material drives flow through a slab– Requires some ad hoc assumptions regarding constitutive equations and

boundary conditions

• Variational approach– S. Baek and A. R. Srinivasa (2004)– Gel is swollen in a bath; can be generalized to other choice of closed system– Provides rigorous underpinning for the requisite constitutive equations and

boundary conditions.

Important Processes

h

1 diffusion

photopolymerization0

2 swelling

3 global shape change

Important Processes: Relevant Parametersh

Mm [A] G0

Pertinent Material Properties

External Stimulus(x,0)

incorporated via

F (x,t)Deformation Gradient Tensor

(x,t)

Inter-Relationships among the Processes

Mm [A] G0

Material Specifications

h

(x,t)

rm (x,t)

I (x,t)

G (x,t)

F (x,t)

jm (x,t)

External StimulusIi (x,t)

Internal VariablesGlobal Shape Change

D

Each arrow is a physical (and, therefore, mathematical) relation

[A]

Diffusion

h

rm (x,t)

I (x,t)

G (x,t)

F (x,t)

External StimulusIi (x,t)

Internal VariablesGlobal Shape Change

Mm

(x,t)

jm (x,t)

D

G0

Material Specifications

1) Diffusion

SwellingMm [A] G0

Material Specifications

h

rm (x,t)

I (x,t)

G (x,t)jm (x,t)

External StimulusIi (x,t)

Internal VariablesGlobal Shape Change

D

(x,t)

F (x,t)2) Swelling

Global Shape Change

Mm [A] G0

Material Specifications

h

(x,t)

rm (x,t)

I (x,t)

jm (x,t)

External StimulusIi (x,t)

Internal Variables

D

G (x,t)

F (x,t)

3) Global Shape Change

• Photosensitive Elastomers for Remote Manipulation– Enable wavefront corrections for static abberrations– Function in air, vacuum and aqueous media– Present interesting theoretical mechanics questions– May find application in “labs-on-a-chip” or space-based optics

Conclusions & Future Directions

Acknowledgements“That Man May See” FoundationChartrand FoundationCalhoun Vision

Robert Grubbs

Chemistry, Caltech

Dan Schwartz

Ophthalmology, UCSF