Biomaterials in ophthalmology
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Rachel Williams University of Liverpool. Biomaterials in Ophthalmology. Anatomy of the Eye. Light comes through the pupil and it refracted by the various media it passes through The image is focused by the lens

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Biomaterials in ophthalmology

Rachel Williams

University of Liverpool

Biomaterials in Ophthalmology


Anatomy of the eye

Anatomy of the Eye

  • Light comes through the pupil and it refracted by the various media it passes through

  • The image is focused by the lens

  • The image is formed on the retina such that the rods and cones are stimulated and nerve pulses are conducted to the cerebral cortex via the optic nerve


Visual defects

Visual defects

  • The lens does not accommodate, therefore it cannot focus the image

  • The lens becomes cloudy, therefore light cannot pass through it

  • The retina cannot pass information to the optic nerve


Where are biomaterials used in the eye

Where are biomaterials used in the eye?

  • Three major areas:

    • Contact lens

    • Intraocular lens

    • Retinal detachment

  • Three major areas:

    • Glaucoma

    • Orbital reconstruction

    • Drug delivery


Contact lenses

Contact lenses

  • Optically transparent

  • Non-irritant to the tissues

  • Adequate mechanical properties

  • Resistant to degradation (particular UV)

  • Ease of manufacture

  • Good wettability

  • High gas permeability

  • Resistant to spoilage and contamination


Wettability the ability of water to spread on a surface

Wettability – the ability of water to spread on a surface

High wettability

Low wettability


Tear film

Tear film

Functions:

  • Keeps the cornea wet which is essential to maintain a clear view and smooth surface

  • Transports gases to and from the cornea

  • Contains bacteriocidal substances

  • Washes away debris

    Contact lenses can affect any of these functions


Gas permeability

Gas permeability

  • Oxygen permeability:

    This is an intrinsic property of the material is a product of the DIFFUSION COEFFICIENT and the solubility of O2 in the material

  • Oxygen transmissibility:

    This is the amount of O2 that will diffuse through the lens in unit time and is

    DIFFUSION COEFFICIENT/thickness


Spoilation

Spoilation

These are deposits which collect on the lens due to its interaction with tear fluids

  • Inorganic components such as calcium or phosphates

  • A protein film that adheres to the lens

  • Fungal or bacterial deposits which feed on the protein film

  • Others such as cosmetics or components of the cleaning fluids


Contact lens materials

Contact Lens Materials

  • Hard contact lenses

    • PMMA

    • Rigid gas permeable

  • Soft contact lenses

    • Hydrogel

    • Silicone

    • Silicone hydrogels


Pmma lenses

PMMA Lenses

  • Good mechanical properties

  • Good manufacturing tolerance

  • Good optical properties

  • Good durability

  • Acceptable wettability

  • Very poor oxygen permeability

C

H3

CH2

C

C

O

O

C

H3


Rigid gas permeable lenses

Rigid Gas Permeable Lenses

C

H3

  • Copolymers of MMA and methacrylate-functionalised siloxane (TRIS)

  • Wettability, oxygen permeability, modulus, hardness controlled by ratio of MMA:TRIS

  • TRIS increases oxygen permeability but reduces wettability

C

C

O

O

C

H3

C

H3

C

H3

Si

OSi(CH3)3

(H3C)3SiO

OSi(CH3)3


Hydrogel lenses

Hydrogel lenses

O

  • Hydroxyethylmethacrylate (pHEMA)

  • N-vinylpyrrolidinone (NVP)

  • Glyceryl methacrylate (GMA)

    • Good wettability

    • Good oxygen permeability (depends on water content)

    • Excellent patient comfort

    • Poor tear strength

    • Tendency to spoil

OH

O

N

O

O

OH

O

OH


Silicone lenses

Silicone Lenses

Dimethylsiloxane

  • Excellent optical properties

  • Good tear resistance

  • High oxygen permeability

  • Low wettability

  • Tendency to bind tear lipids

  • Tendency to adhere to cornea

CH3

Si

O

O

CH3

n


Silicone hydrogel lenses

Silicone hydrogel Lenses

  • Based on

    • high oxygen permeability of PDMS

    • High wettability of hydrogel

    • Excellent patient comfort of hydrogel

    • Good mechanical properties of PDMS


Cataracts

Cataracts

  • Most common treatable form of blindness throughout the world

  • Removal of crystalline lens

  • Replacement with IOL


Iol implantation

IOL implantation


Iol materials

IOL Materials

R=CH3

Or H

CH3

CH3

R

CH3

C

CH

C

CH

C

CH

Si

O

C

O

C

O

C

O

CH3

O

O

O

Poly(dimethyl siloxane)

PDMS

CH3

CH2

CH2

CH2

CH2

Poly(methyl methacrylate)

PMMA

OH

Poly(hydroxyethyl methacrylate)

PHEMA

Phenylethyl methyacrylate

Phenylethyl acrylate

PEMA/PEA

Acrylics


Development of pco

Development of PCO

Anterior capsule

Residual LEC

IOL

haptics

Posterior capsule

  • Two approaches to inhibit PCO:

  • Inhibition of the LEC onto the posterior capsule behind the IOL

  • Enhancement of a monolayer of LEC with the natural phenotypic morphology to encourage the formation of an IOL/LEC/Posterior capsule sandwich.

IOL

Capsular wrinkling


Retinal detachment

Retinal Detachment

Aim to reposition retina on underlying tissue

  • Push the sclera in towards detached retina

  • Push retina out towards sclera


Scleral buckle

Scleral buckle

  • Silicone elastomer band or sponge

  • Cryotherapy


Tamponade agents for retinal detachments

Tamponade agents for retinal detachments

Tamponade agent:

Air

Expanding gases

Silicone oil

perfluorocarbon liquids

semifluorinated alkanes

Retinal tear


Important properties of tamponade agents

Important properties of tamponade agents

  • Interfacial energies

  • Specific gravity

  • Viscosity


Existing tamponade agents

Specific gravity

[g/cm3]

Interface Tension at 25°C against water [N/m*10-3]

Visco

[cSt]

Perfluorooctane

1.40

55.0

1.76

F6H8

1.35

49.1

2.5

Silicone oil (5000)

0.97

35.4

5000

F6H8-Si Oil mix

1.04-1.08

?

1100-1900

Existing tamponade agents

  • Air or other gases

  • Silicone oil

  • Perfluoroctane

  • F6H8

  • F6H8/silicone oil mixtures


Model eye

Model eye

  • Cylindrical model

  • Constructed of perspex

  • Input and output ports

  • Initially filled with a protein solution to render internal surface hydrophilic

  • Sequential replacement of protein solution with tamponade agent


Silicone oil

Silicone oil


Biomaterials in ophthalmology

F6H8


F6h8 silicone oil mixtures

F6H8/Silicone oil mixtures


Indented model

Indented model

F6H8

F6H8/silicone oil mixture


Emulsification

Emulsification


Increase emulsification resistance

Increase emulsification resistance

  • Hypothesis

    • The addition of a high molecular weight silicone polymer to silicone oil will increase the extensional viscosity and increase emulsification resistance


Shear and extensional viscosity

extensional

Viscosity

shear

Log strain rate

Shear and extensional viscosity

Extensional viscosity is a measure of the ‘stringiness’ of the fluid

Shear viscosity is a resistance to flow


Silicone oil 1000 high mw additive blends extensional viscosity vs strain rate

Silicone Oil 1000 / high MW additive blendsExtensional viscosity vs. strain rate


Silicone oil 1000 high mw additive blends shear viscosity vs strain rate

Silicone Oil 1000 / high MW additive blendsShear viscosity vs. strain rate


Injection into the eye

Injection into the eye


Transplantation of rpe

Transplantation of RPE

  • Clinical problem

    • Age-related macular degeneration

  • New route for clinical treatment

    • Transplantation of RPE


Rpe transplantation for the treatment of amd

[www.eyesight.org]

[www.ahaf.org]

[www.ahaf.org]

RPE transplantation for the treatment of AMD


Operative procedure

Operative procedure

  • A monolayer of RPE/IPE are grown on a substrate in culture

  • Replace diseased RPE and underlying tissues sub-retinally

  • Unroll the substrate and monolayer of cells and replace retina placing macular on healthy tissue


Rpe transplant substrates

RPE transplant substrates:

Requirements:

Substrates must:

  • replace native damaged Bruch’s membrane

  • support a monolayer of functional RPE cells

    Physical properties required:

  • biostability so it can remain for the patient lifetime and support and protect the cells

  • flexibility so it can be folded to minimise implantation trauma

  • thin films to minimise distortion but sufficiently robust for handling

  • porosity to maintain transport of nutrients and waste

ePTFE


Eptfe membranes

F

F

F

F

F

F

F

[-C-C-C-C-C-C-C]n

F

F

F

F

F

F

F

F

F

*

*

*

*

*

[-C-C-C-C-C-C-C]n

F

F

F

F

F

F

F

HO

H O

HO

HO

HO

F

F

[-C-C-C-C-C-C-C]n

F

F

F

F

F

F

F

ePTFE membranes

H2O

NH3(g) plasma


Cell adhesion

Cell adhesion

Untreated

Plasma treated


Summary

Summary

RPE transplantation

Contact lenses

Intraocular lenses

Tamponade agents


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