Julie Kornfield, Bob Grubbs

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Sculpting Implants in situ Light-Adjustable
Intraocular Lens
Julie Kornfield, Bob Grubbs Division of
Chemistry Chemical Engineering, Caltech
Jagdish Jethmalani Chris Sandstedt Calhoun
Vision
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Motivation
The Problem Imperfections in wound healing and
lens positioning create refractive errors
(farsightedness, nearsightedness and astigmatism).
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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.

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Design Principles for New Polymers
Photopolymerizable end groups
Photoinitiator (Light sensitive)
gt
-Low glass transition temperature (-125?
C) -Relatively rapid diffusionÆability to modify
shape on large length scale
-Non-volatile -Insoluble in water
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Light-induced changes in shape and refractive
index
Spatially resolved irradiation
"locking"
gt
gt
Irradiation profile controlled by - Transmission
mask, - Spatial light modulator, or - Rastered
laser
- Once the desired shape is achieved, blanket
irradiation makes it permanent
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Simple Characterization of Lenses

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

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Example of Power Change
Ronchi Interferogram Before Irradiation Lens
quality matches current IOLs
Ronchi Interferogram After Irradiation
Irradiate 2 min with 2 mW/cm2 at 325nm, allow 3
hr for diffusion Focal length reduced from 11mm
to 4mm!
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Adjustments occur Overnight
time post irradiation (hours)

• 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.

Experiments performed at Calhoun Vision.
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Biocompatibility of Material Irradiation in
vivo evaluation in rabbit
Two weeks after surgery and irradiation, the eye
is quiet.
Explanted lens for evaluation.
Calhoun Vision and Dr. Nick Mamalis at the
University of Utah, Salt Lake City, Utah
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Adjustments in vivo are Precise and Predictable
Animal-to-animal variability is small.
Dose-response relationship measured in the lab
holds in vivo, too.
Calhoun Vision and Dr. Nick Mamalis at the
University of Utah, Salt Lake City, Utah
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Precise Myopic, Hyperopic Astigmatic Adjustments
Control orientation magnitude.
Dose-Response Experiments performed at Calhoun
Vision.
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Clinical Implementation
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

Developed by Zeiss Meditec and Calhoun Vision.
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Digital Mirror Device Projects Any Desired
Intensity Profile
To decrease lens power
To Increase lens power
To correct astigmatism
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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

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Results in Clinical Trials

• Precise, predictable adjustments are achieved in
  patients.

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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)
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Restoring Distance Near Vision
From the Eye Sight website of student Kyle Keenan
at Steton Hall University.
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Strategies for Built-in Bifocals

• Multizone lens

Diffractive lens on a Refractive lens
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Irradiate to Add Multiple Zones
1.9 mm central region 0.5 mm ring 2.3 D
2.0 mm central region -2.5 D and 0.6 mm ring
2.8 D
Alternating Zones of 2 D
1.8 mm central region 0.6 mm ring 2.8 D
Experiments performed at Calhoun Vision.
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Irradiate to Add a Diffractive Lens
Irradiance Profile
Wavefront Image
Phase Contrast Microscope Image
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USAF Target Images
Calhoun 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
Near Focus G4 E2
Distance Focus G4 E3
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Irradiation Patterns

• Non-linear Response Complicated Profiles
• Currently empirical

Cylinder
Tetrafoil
Need for a theoretical model for systematic
design.
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Predicting Shape ChangeIs 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

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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

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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.

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Important Processes
hn
global shape change
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Important Processes Relevant Parameters
hn
f (x,t)
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Inter-Relationships among the Processes
Material Specifications
hn
Mm c f0 A G0
External Stimulus Ii (x,t)
D
I (x,t)
f (x,t)
rm (x,t)
jm (x,t)
G (x,t)
F (x,t)
Global Shape Change
Internal Variables
Each arrow is a physical (and, therefore,
mathematical) relation
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Diffusion
hn
A
External Stimulus Ii (x,t)
1) Diffusion
I (x,t)
rm (x,t)
G (x,t)
F (x,t)
Global Shape Change
Internal Variables
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Swelling
Material Specifications
hn
Mm c f0 A G0
External Stimulus Ii (x,t)
D
I (x,t)
rm (x,t)
jm (x,t)
G (x,t)
2) Swelling
Global Shape Change
Internal Variables
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Global Shape Change
Material Specifications
hn
Mm c f0 A G0
External Stimulus Ii (x,t)
D
I (x,t)
f (x,t)
rm (x,t)
jm (x,t)
G (x,t)
F (x,t)
3) Global Shape Change
Internal Variables
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Conclusions Future Directions

• 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

Acknowledgements

• Robert Grubbs
• Chemistry,
• Caltech

• Dan Schwartz
• Ophthalmology, UCSF

That Man May See FoundationChartrand
FoundationCalhoun Vision