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Biomaterials in Ophthalmology

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

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  1. Rachel Williams University of Liverpool Biomaterials in Ophthalmology

  2. 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

  3. 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

  4. Where are biomaterials used in the eye? • Three major areas: • Contact lens • Intraocular lens • Retinal detachment • Three major areas: • Glaucoma • Orbital reconstruction • Drug delivery

  5. 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

  6. Wettability – the ability of water to spread on a surface High wettability Low wettability

  7. 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

  8. 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

  9. 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

  10. Contact Lens Materials • Hard contact lenses • PMMA • Rigid gas permeable • Soft contact lenses • Hydrogel • Silicone • Silicone hydrogels

  11. 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

  12. 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

  13. 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

  14. 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

  15. Silicone hydrogel Lenses • Based on • high oxygen permeability of PDMS • High wettability of hydrogel • Excellent patient comfort of hydrogel • Good mechanical properties of PDMS

  16. Cataracts • Most common treatable form of blindness throughout the world • Removal of crystalline lens • Replacement with IOL

  17. IOL implantation

  18. 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

  19. 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

  20. Retinal Detachment Aim to reposition retina on underlying tissue • Push the sclera in towards detached retina • Push retina out towards sclera

  21. Scleral buckle • Silicone elastomer band or sponge • Cryotherapy

  22. Tamponade agents for retinal detachments Tamponade agent: Air Expanding gases Silicone oil perfluorocarbon liquids semifluorinated alkanes Retinal tear

  23. Important properties of tamponade agents • Interfacial energies • Specific gravity • Viscosity

  24. 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

  25. 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

  26. Silicone oil

  27. F6H8

  28. F6H8/Silicone oil mixtures

  29. Indented model F6H8 F6H8/silicone oil mixture

  30. Emulsification

  31. 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

  32. 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

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

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

  35. Injection into the eye

  36. Transplantation of RPE • Clinical problem • Age-related macular degeneration • New route for clinical treatment • Transplantation of RPE

  37. [www.eyesight.org] [www.ahaf.org] [www.ahaf.org] RPE transplantation for the treatment of AMD

  38. 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

  39. 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

  40. 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

  41. Cell adhesion Untreated Plasma treated

  42. Summary RPE transplantation Contact lenses Intraocular lenses Tamponade agents

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