julie kornfield, bob grubbs division of chemistry & chemical engineering, caltech
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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
==
>
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
==
>
- Once the desired shape is achieved, blanket irradiation makes it permanent
==
>
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
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: 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
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