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New technology in contact lens materials
New Technology in Contact Lens Materials Noel A. Brennan*
Introduction During the centenary celebration of the first fitting of contact lenses to the eye, it is interesting to reflect upon the developments in contact lens materials during that time. Despite the rapid increase in usage of contact lenses over the past forty years, and the major investment in research and development over the past twenty years, there have really been only two materials that have enjoyed marketplace leadership. Polymethylmethacrylate (PMMA) was essentially the only material widely used pre 1960 and it retained the major proportion of the marketplace until the early seventies when hydroxyethylmethacrylate (HEMA) became popular. Soft, HEMA based materials are still the most frequently used, despite the obvious disadvantages that these lenses present. It is remarkable that this material which was first cast into contact lenses some thirty years ago in a kitchen laboratory still enjoys market leadership, in the context of the major advances over the -last twenty years both in our understanding of the eyecontact lens interaction and in contact lens manufacturing technology. Although the so-called 'siloxane-acrylate' materials have gained in popularity recently, they appear unlikely to replace HEMA as the biggest selling material (Schwartz, 1988), and it remains to be seen whether the fluoro'siloxane-acrylates, pure fluoropolymers or some other material will overtake HEMA in terms of market leadership. Certainly, contact lens material development technology has 'grown-up' in that the selection procedure for experimenting with new materials is no longer performed on a trial and error basis, but is part of a well *Department of Optometry, University of Melbourne, Parkville, Australia 3052.
Transactions BCLA International Conference 1988
considered approach attempting to reach a balance between desirable material properties. Until recently, the major driving force behind new material development has been the desire to achieve high oxygen permeability, since the cornea requires oxygen from its external boundary for normal metabolic function, a minimum flow of oxygen must be maintained through a contact lens for it to be worn without compromising corneal physiology. In recent times, we have seen a number of controversies surrounding both the oxygen level required for normal corneal function, and the ability of contact lens materials to permit the passage of oxygen~ Two vital pieces of information appear to have emerged from the ensuing debates regarding oxygen supply; firstly, materials which 'rely on water as the conductive medium for the passag6 of oxygen cannot provide sufficient oxygen to maintain the cornea in its normal state during closed eye wear; and secondly, some of the new rigid gas-permeable (RGP) materials can satisfy the corneal oxygen needs even during closed eye wear. Although the oxygen permeability debate has created confusion for both industry and practitioners, the argument has been essential for quantifying both the basic requirements of the cornea and the ability of a contact lens to meet those needs. The :major bout of infective corneal ulceration associated with extended wear of contact lenses in the United States is evidence enough of the effects that compromise of the corneal requirements can bring about. With the 'Dk barrier' essentially behind us, we can now get on to the serious business of meeting the other requirements of contact lenses, remembering that all other advances must be achieved without compromise to the passage of oxygen through the material. In this paper, the specific properties of contact lens materials that require further investigation and the way in which these particular attributes cart be imparted without compromise to other material properties will be considered. This information will then be used as a background for discussing the various options available to the material scientist for the manufacture of contact lenses, and the advantages of the various types of materials which are currently available or being developed.
Material Properties A long list of material properties that should be considered before deciding that a particular material is suitable for contact lenses has been presented by Peppas and Yang (1981). Of these properties, there are three which are currently being closely investigated. Other properties are considered to be either easy to achieve or of little apparent importance. The purpose of this paper is to discuss these three specific properties.
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Mechanical Properties Although there is a diverse array of procedures for testing specific aspects of the mechanical properties of materials, the application of results from these tests is often confusing. From the available data, a number of general comments may be drawn. The mechanical properties will very much determine the type of lens design that ultimately needs to be used. For instance, a material with a very low modulus of elasticity (a soft lens) will drape over the cornea, and is often used with a large diameter design. These lenses cannot be made too thin or they will be fragile. On the other hand, a material with a high modulus of elasticity (a hard lens) will be fitted according to fluorescein patterns, and usually in a small diameter design. Materials in between these extremes may have sufficient mechanical strength to produce a suction type effect on the cornea (eg silicone lenses, although a wettability factor may also be at play). Another important aspect of lens design with regard to material properties is the achievement of adequate tear exchange under the lens. For example, soft lenses must be fitted very fiat to achieve good exchange of tears for the removal of debris. Another example is the design of toric lenses, which must be different for hard and soft materials. Matching lens design to mechanical properties of a material is probably the most challenging aspect of achieving the 'ideal' contact lens yet to be fully confronted. One factor relating to lens mechanical properties that has received much attention of recent is the flexure of RGP lenses on the eye. Where a material is too flexible, corneal toricity can encourage bending of the lens upon insertion due to the capillary effects of the tears, and further bending during the blink due to the forces of the lids. Again, material design is of the utmost importance, and, according to recent work by Fatt (1988), is of greater importance than the modulus of elasticity of the material itself. The degree to which a fiat slab of material will distort is dependent upon the first power of the modulus,-but the third power of the thickness and the third power of the diameter. The modulus of elasticity varies only by a factor of two between the most flexible and the least flexible materials available on the market
today, and ~ difference can be easily accounted for by using a slightly thicker, slightly larger lens. As an example, an increase of about 17% in thickness (say, from 0.15 to 0.175 ram) and 8% in diameter (from 9.0 to 9.7 ram) produces a 100% increase in the 'stiffness' of a lens. Since we are principally concerned with negative power lenses which thicken toward the periphery, the increase in thickness and diameter may not even need be this big. The conclusion from Fart's work is that the modulus of elasticity is of minor concern as a property of RGP materials, and that lens design is the critical factor. Mechanical properties also become of great importance in the consideration of lens fabrication. Certain materials cannot be lathed, which places restrictions on lens designs, may increase the cost of manufacture, and means that all lenses must be delivered from the central place of production. Wettability . A major prerequisite of a material for use in contact lenses is the ability of the material to hold a stable tear layer. A surface which does not wet does not allow adequate refraction of light and so may decrease the wearer's vision, as well as allowing drying of the proteins on the surface which may lead to deposit formation. Many of the general concepts of wettability have previously been reviewed by Fatt (1984). A number of important points are borne out in his paper. Fatt stated that the concept of wettability has no real correlate in scientific terms. One may speak of a contact angle, which may be taken as a measure of hydrophilicity of a surface. A wet'table material will have a low contact angle, and a non-wettable surface will have a high contact angle. However, a variety of techniques exist for the measurement of contact angle (Sessile drop, Captive Bubble, Wilhelmy Plate), and the practitioner is confronted with many different values of contact angles for contact lens materials. It is often difficult to determine how a contact angle measurement has been achieved, which method produces clinically applicable results, and whether results from different investigators can be compared. A major difference exists in advancing angle versus receding angle measurements. When a drop of liquid is
Remove Liquid
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Advancing Angle Fig. 1, The contact angle 0 of a drop of liquid on a surface increases momentarily if more liquid is added, The shape of the drop reaches equilibrium with the liquid contacting the surface at an angle equal to the
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Receding Angle
advancing contact angle. Removal of some of the liquid decreases the angle of contact, and equilibrium is reached at a new contact angle, the receding angle.
Transaction5 BCLA tnu:rna6onat Cc,nference 1988
placed on the surface of a material, the angle that the edge of the drop makes with the surface, the contact angle, is determined by the interfacial tension. If a small amount of liquid is added to the drop, the angle will temporarily increase and the drop will spread until equilibrium is again reached, when the contact angle will be the same as for the smaller drop. This is known as the advancing angle. This concept is illustrated in Figure 1. If some of the liquid is now removed,, the contact angle will decrease and the area of the drop in contact with the surface will shrink until a new equilibrium is reached. However, it is noteworthy that the contact angle at equilibrium is now very much different to the advancing angle, this new angle is termed the receding angle, and it will usually be significantly lower than the advancing angle.
The portion of the surface of the material that was covered by the liquid has undergone a change in surface energy; it is essentially more hydrophilic. This phenomenon is known as hysteresis (Lambert et al, 1985), and will occur to different extents in different materials depending upon the chemical structure of the material. When a liquid is in contact with the surface the more hydrophilic groups are attracted to the surface, for example the hydroxyl groups in HEMA material in Fig 2. However, when air is in contact with the surface, the hydrophilic groups are attracted more towards the inside of the material, and hence, for HEMA, the more hydrophobic methyl groups are turned towards the surface. A material with a more rigid structure, such as PMMA will show less hysteresis, and consequently, less difference in advancing and receding angles. Currently popular RGP materials show considerable hysteresis, and consequently, will be more hydrophilic following storage in liquid media. The phenomenon justifies the practice of using wetting drops, and of the need to store RGP materials in liquid, whereas PMMA may be stored dry. It also stands to reason that where the tears consistently break over the front surface of a material in vivo, the hysteresis phenomenon will aggravate the problem by making the surface less 'wettable'. Despite the attention giving to contact angles, and th~ importance of material hysteresis, contact angles measured in vitro are of little use for the prediction of wetting performance in the eye. A chemical property of
a surface is that it must be in equilibrium with the medium which surrounds it. Even a 'clean' surface, when placed into a near vacuum will attract minute particles of dust from that atmosphere. So when a lens is placed in the eye, the surface will come into equilibrium with the tear fluid by a build up of tear constituents until the chemical potential of the particles in the tears equals the potential of those on the surface. As well as being an important factor in the build-up of lens deposits (see below), this means that the surface properties will change. The coated lens may have totally different wetting properties to the uncoated lens. Benjamin and co-workers (1986) has demonstrated this effect by measuring the contact angle of drops of saline placed onto lens whilst being worn by patients in the supine position. As expected, the contact angle changes dramatically following blinking by the patient, as the surface becomes coated with constituents from the tears. The coating serves to improve the wettability of the material. This .simple experiment demonstrates the futility on in vitro contact angle measurements for predicting in eye wettability of a lens. Clinically, the wettability of a contact lens is best judged by simple observation techniques, such as break-up time measurements with either the biomicroscope, keratometer or placido disc. Since the average blink rate may commonly fall as low as 5 per minute during periods of concentration, the break-up time should not be less than 12 seconds or the lens will not be completely wet. The characteristic of lens materials that makes them wettable is a negatively charged surface. In effect, the surface of all materials when placed in solution will take on a relative negative charge, and the degree of this charge is what will determine the extent of wetting. Incorporation of methacrylic acid into the polymer has been found to be successful for improving in vivo wetting performance. However, this serves to increase the attraction of lysozyme to the surface and other more suitable wetting agents need to be explored. Resistance to Surface Deposition One of the major difficulties for both patients and clinicians is accumulation of material from the tear layer on the lens surface. Surface deposits may affect vision and wetting, and provide a stimulus to an
AIR
~CH2-CH2\ CH2-CH2~ OH LENS OH Fig. 2. When the surface of a H E M A lens is in contact with air, the hydrophobic methyl groups of the chain are exposed at the surface. When the surface is in aqueous
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Conference
1988
CH2-CHJ CH 2-CH!OH LENS medium, the hydrophilic hydroxyl groups are oriented towards the surface. This phenomenon is known as hysteresis.
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immunological reaction. There is the potential for each of the tear constituents to adsorb to the surface of a contact lens, and proteins, lipids, glycoproteins, calcium and other environmental matter have been found in accumulations of deposit, the principal offender is protein, of which lysozyme, lactoferrin, albumin (tear specific), pre-albumin, PMFA, immunoglobin comprise the bulk. Adsorption of protein to a.material surface is a complicated matter. A great deal may be learnt from studies of the adsorption characteristics of biomaterials used for artificial vessels and valves. Whilst blood is significantly more complicated to study than tear fluid, containment of protein adsorption during contact lens wear presents the additional challenge of dealing with an air interface. A s detailed above, the potential of a particular species within solution must equal the potential of the species at the surface. Thus a certain amount of material deposition will always occur when a lens is covered by the tear film. Physical evidence of this aggregation has been observed with the electron microscope (Fowler and Allansmith, 1980). Where a species remains unchanged in its conformation u p o n adsorption, equilibrium will eventuate with minimal build-up on the surface. However, in some cases, the species will change in conformation upon adsorption and will not contribute to the chemical potential so far as the original species goes. This means that more of the species will be attracted to the surface, only to change in conformation and so the process will continue. The concept is illustrated in Fig 3. Further complications arise if the second and third layer which are laid down change in conformation in a different manner to the first layer. The use of attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) allows the deposited material to be identified and conformation of adsorbed proteins to be ascertained
(Castilto et al, 1984). Both lysozyme and albumin typically change from a predominantly 0~-helix conformation to a 13-sheet conformation on contact with the surface of a contact lens. A wide variety of factors influence the degree to which specific proteins WIUbe attracted to the surface of a material. In a number of cases, simplistic models of protein adsorption have been proposed. For example, methacrylic acid (MAA) is often incorporated into a material to increase the wettability. The inclusion of MAA contributes to an increase in the negative surface charge, which then attracts lysozyme, which is the only positively charged protein to be found in any quantity in the tears. Whilst the inclusion of MAA does increase the adsorption of lyso~me dramatically, there are many other factors aside from simple electrostatic attraction in the explanation of the increased surface build-up. The following list of forces and bonds which may occur during protein accumulation is a testimony of the complexity of the phenomenon (Absotom et al, 1984; Sharma, 1984): London dispersion forces, hydrogen bonds, dipole-dipole interaction, donor acceptor bonds, electrostatic interactions, acid-base bonds, biochemicals interactions (ligand-receptors), Van der Waals forces, Keesom forces, Debye-Falkenhagen forces. Given that a wide range of factors operate in the attraction and binding of proteins to a lens surface, relatively few specific properties of the lens material play a role. The charge of the surface is an important variable. All surfaces acquire a negative charge when placed in aqueous medium, but the extent of this charge will vary between materials. Pure silicone has little charge, and consequently, does not adsorb a great degree of protein. Furthermore, that protein which is attracted is relatively easy to move. More highly charged surfaces will bind protein tenaciously. It is of interest to note that less wet-table surfaces bind little protein,
®
®®
®
®
®
® surface
Fig. 3. The molecules of species A in solution are at equilibrium with the molecules on the surface. If conformational changes occur to species A on contact
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iii iiiiiiiiii!iiiil
® ®
solution
® ® ® ® solution
surface
with the surface such that a new chemical entity is formed, species B, then more molecules of species A are attracted to the surface to attain equilibrium.
Transactions BCLA [ntc,"nationa! Conference 1988
whereas more highly charged, wettable surfaces suffer protein build-up. This scientific reasoning contrasts with the clinical observation and the known phenomenon of protein degradation upon drying. Material composition is another important variable. The basic constituents may have specific attraction for certain molecules, especially where these constituents are impurities not removed during the manufacturing process. In corporation of fluorine into a material has the effect of reducing protein aggregation. Furthermore inhomogeneity within a material can create regions with greater affinity to protein deposition. Surface irregularities contribute to adsorption presumably by increasing the surface area, and by providing sites which allow greater capacity for permanent binding.A recent laboratory study found that lathe cut lenses bind approximately twice as much protein as spun-cast lenses (Castillo et al, 1986). The accumulation of protein occurs selectively with competition between different components for binding sites. The charge on the protein is one aspect of the species which determines the composition of surface build-up. Lysozyme has a positive charge, and is thus attracted to the negative charge on a lens surface. Other characteristics of the protein species which influence accumulation include the molecular weight and size, and obviously the concentation of the species in the tears. Patient characteristics must also be involved in protein accumulation since some wearers can go for years without deposition, where others continually 'lay down' protein. Tear pH, osmolarity and temperature are some relevant variables. The ability of the tears to wet the lens surface is another likely contributing factor, drying contributing to greater protein degradation. Another consideration is the frequency and force of the blink, since agitation increases the amount of protein bound to the surface. The preceding discussion has focused on protein adsorption. Protein is also adsorbed, and the involvement of this protein in creating immunological stimuli is not certain. Lysozyme can enter the matrix of most soft lens materials, and apparently attaches to the chains without any obvious side-effects. Albumin is not absorbed into lower water content materials but will enter the matrix of higher water content materials, where the pore size is considerably larger. It is apparently for this reason that higher water content materials can not be thermally disinfected without suffering discoloration. Globulins are too large to enter most available hydrogels. Since protein adsorption can not be avoided, material optimisation needs to be based on developing a surface which will attract 'desirable' proteins with minimal conformational change. The corneal surface attracts mucin to the surface which makes the surface wettable without build-up of protein. A lens surface which attracts mucopolysaccharides in this way would obviously be a great advantage.
Transactions BCLA International Conference 1988
Options in Material Production From the drawing board to the final lens product, the material scientist has a wide range of factors which may be varied but must be controlled to produce the 'ideal' polymer. The choice of monomer to be polymerized and thus form the backbone of the material will determine a number of the material properties. Methyl methacrylate gives a material with great mechanical stability, but poor oxygen permeability. Silicone groups reduce the mechanical strength and the wettability but add to the oxygen permeability. Fluorine adds to the oxygen permeability and the wettability but may adversely effect the mechanical properties. Cross-linking agents need to be added to provide strength to the material. These will determine the hydration of hydrogel materials, and also influence the wettability. Wetting agents can also be added, but these need to be balanced against their protein adsorption capacity, and the other effects that they are likely to have. For instance, methacrylic acid is often added to increase" wettability, however, its presence strongly attracts build up of the tear protein, lysozyme. Between methods, the regularity of polymerization, retention of by-products and speed of reaction will vary. Radiation polymerization encourages homogeneity in the degree of polymerization throughout the material, although bulk polymerization is an easier process. The above v~/riations will produce materials with differing degrees of crystallinity. The method of lens fabrication will be varied depending upon the properties of the material. Although the majority of lenses are lathe cut, allowing greater flexibility in design, it may not be possible to cut the material in this way because of its physical properties. Cast or injection molding or spin casting may provide greater reproducibility or may simply be necessary because the material cannot be lathed. All of the factors mentioned so far will affect the final surface quality of a lens. In particular, the method of lens fabrication will have a significant effect on the properties of the surface. However, it is possible through a variety of techniques to add a surface coat to produce a variety of surface properties. These may be induced by both chemical and radiation means. Despite the ability to control the above variables in material production, there are a number of factors which remain uncontrollable. These include impurities in the bulk material, failure to totally eliminate the byproducts, the random nature of polymerization, and the viscosity, degree of agitation and heat transfer during the polymerization prodecure. These factors lead to variation in the material properties between batches of the same material. .Recently, there have been reports of surface treatments which reduce protein build-up. Oxygen plasma treatment improved both the wettability and protein resistance of a rigid gas permeable lens surface (Hough and Patel, 1986). Another chemical surface treatment has made the Hydrocurve 55 % water content material significantly more resistant TM
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to protein build-up without interfering with other material characteristics (Manrique, 1987). More widespread use of surface treatments should occur as new technology in surface chemistry is incorporated into contact lens manufacture. Discussion The recent court action in the United States which reduces the number of major manufacturers researching new lens materials may retard the development of new technology in contact lens material production. On the other hand, the restrictions on the use of current concepts may instigate research into new areas of material development. A review of patent applications, however, indicates that most of the recent apph'cations have been for materials based on fluorosiloxane acrylate materials, not dissimilar in basic sturcture to the Equalens which is currently being marketed. The current trend for increasing use of hard-gas permeable materials is expected to continue. Where the past few years have seen growth in the area of siloxane acrylate materials, the next few years will see increasing sales of materials containing fluorine. These materials have good oxygen permeability, good wettability and reasonable resistance from protein accumulation, but variable dimensional stability. The incorporation of methacrylic acid as a wetting agent in these materials means that lysozyme deposition is still a likely occurrence. •The pure fluoropolymer material produced by 3M and marketed by Allergan is likely to have a major impact on the industry over the coming years. It has high oxygen permeability, good wettability and freedom from protein build-up, the major disadvantage with the material is its poor machinability, which requires distribution from large central manufacturing centres and limitations to the range of parameters.
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As more sophisticated polymer technology is incorporated into contact lens development, we should see increasing use of surface treatments on base structures with more desirable mechanical properties and a high level of oxygen permeability. Soft lens materials which contain low amounts of water, but with high oxygen permeability is another exciting advance which should also be introduced at some time in the future. Meanwhile, lens fitters should continue to improve lens design to the extent that torics and bifocal contact lenses can be fitted with simplicity. References Absolom, DR, Zingg W, Van Oss CA,Neumann AW. (1984) Protein and platelet interactions with polymer surfaces. Biomat Med Dev Art Org 12: 235-266. Benjamin WJ, Yeager MD, Desai NN, Carmichael CA. (1986) In vivo analysis of contact angles. Int Eyecare 2: 163-170. Castillo EI, Koenig JL, Anderson JM, Kliment CK, Lo L (1984) Surface of analysis of biomedical polymers by attenuated total reflectance -- Fournier transform infrared. Biomaterials$: 186193. Castfllo EJ, Koenig JL, Anderson JM. (1986).Characteri/.ation of protein adsorption on soft contact lenses IV Comparison of in vivo spoilage with the in vitro adsorption of tear proteins. Biomaterials 7: 89-96. Fatt I. (1984) Prentice medal lecture. A m l Optom Physiol Opt61: 419-430. Fatt I. (1988) Personal communication. Fowler SA, Allansmith MR. (1980) The surface of continuously worn contact lenses Arch Ophthalmot98: 1233-1236. Hough DA, Patel KID. (1986) Case report. Plasma modification of GPH lenses -- an unexpected clinical result, l Brit Contact Lens Assoc 9: 38-40. Lambert DW, Sibley M, Dabezies OH. (1985) Wetting. In Contact Lenses. The CLAO Guide to Basic Science and Clinical Practice, ed Dabezies OH, pp 8.1-8.13. Manrique J. (1987) Hydrocurve Elite ~ ...The rendering of soft lenses soil resistant. Contemporary Optom 6: 9-13. Peppas NA, Yang W-H M. (1981) Properties-based optimisation of the structure of polymers for contact lens applications. Contact Intraoc Lens MealJ7: 300-313. Schwartz CA. (1988) Technology spurs gowth. Contact Lens Forum 13: 42-49. Sharma CP. (1984) Surface-interface energy contributions to blood compatibility. Biomat Med Dev Art Org 12: 197-213.
Transa.-'tions 8CLA International Cordcreac~ 1988
Introduction During the centenary celebration of the first fitting of contact lenses to the eye, it is interesting to reflect upon the developments in contact lens materials during that time. Despite the rapid increase in usage of contact lenses over the past forty years, and the major investment in research and development over the past twenty years, there have really been only two materials that have enjoyed marketplace leadership. Polymethylmethacrylate (PMMA) was essentially the only material widely used pre 1960 and it retained the major proportion of the marketplace until the early seventies when hydroxyethylmethacrylate (HEMA) became popular. Soft, HEMA based materials are still the most frequently used, despite the obvious disadvantages that these lenses present. It is remarkable that this material which was first cast into contact lenses some thirty years ago in a kitchen laboratory still enjoys market leadership, in the context of the major advances over the -last twenty years both in our understanding of the eyecontact lens interaction and in contact lens manufacturing technology. Although the so-called 'siloxane-acrylate' materials have gained in popularity recently, they appear unlikely to replace HEMA as the biggest selling material (Schwartz, 1988), and it remains to be seen whether the fluoro'siloxane-acrylates, pure fluoropolymers or some other material will overtake HEMA in terms of market leadership. Certainly, contact lens material development technology has 'grown-up' in that the selection procedure for experimenting with new materials is no longer performed on a trial and error basis, but is part of a well *Department of Optometry, University of Melbourne, Parkville, Australia 3052.
Transactions BCLA International Conference 1988
considered approach attempting to reach a balance between desirable material properties. Until recently, the major driving force behind new material development has been the desire to achieve high oxygen permeability, since the cornea requires oxygen from its external boundary for normal metabolic function, a minimum flow of oxygen must be maintained through a contact lens for it to be worn without compromising corneal physiology. In recent times, we have seen a number of controversies surrounding both the oxygen level required for normal corneal function, and the ability of contact lens materials to permit the passage of oxygen~ Two vital pieces of information appear to have emerged from the ensuing debates regarding oxygen supply; firstly, materials which 'rely on water as the conductive medium for the passag6 of oxygen cannot provide sufficient oxygen to maintain the cornea in its normal state during closed eye wear; and secondly, some of the new rigid gas-permeable (RGP) materials can satisfy the corneal oxygen needs even during closed eye wear. Although the oxygen permeability debate has created confusion for both industry and practitioners, the argument has been essential for quantifying both the basic requirements of the cornea and the ability of a contact lens to meet those needs. The :major bout of infective corneal ulceration associated with extended wear of contact lenses in the United States is evidence enough of the effects that compromise of the corneal requirements can bring about. With the 'Dk barrier' essentially behind us, we can now get on to the serious business of meeting the other requirements of contact lenses, remembering that all other advances must be achieved without compromise to the passage of oxygen through the material. In this paper, the specific properties of contact lens materials that require further investigation and the way in which these particular attributes cart be imparted without compromise to other material properties will be considered. This information will then be used as a background for discussing the various options available to the material scientist for the manufacture of contact lenses, and the advantages of the various types of materials which are currently available or being developed.
Material Properties A long list of material properties that should be considered before deciding that a particular material is suitable for contact lenses has been presented by Peppas and Yang (1981). Of these properties, there are three which are currently being closely investigated. Other properties are considered to be either easy to achieve or of little apparent importance. The purpose of this paper is to discuss these three specific properties.
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Mechanical Properties Although there is a diverse array of procedures for testing specific aspects of the mechanical properties of materials, the application of results from these tests is often confusing. From the available data, a number of general comments may be drawn. The mechanical properties will very much determine the type of lens design that ultimately needs to be used. For instance, a material with a very low modulus of elasticity (a soft lens) will drape over the cornea, and is often used with a large diameter design. These lenses cannot be made too thin or they will be fragile. On the other hand, a material with a high modulus of elasticity (a hard lens) will be fitted according to fluorescein patterns, and usually in a small diameter design. Materials in between these extremes may have sufficient mechanical strength to produce a suction type effect on the cornea (eg silicone lenses, although a wettability factor may also be at play). Another important aspect of lens design with regard to material properties is the achievement of adequate tear exchange under the lens. For example, soft lenses must be fitted very fiat to achieve good exchange of tears for the removal of debris. Another example is the design of toric lenses, which must be different for hard and soft materials. Matching lens design to mechanical properties of a material is probably the most challenging aspect of achieving the 'ideal' contact lens yet to be fully confronted. One factor relating to lens mechanical properties that has received much attention of recent is the flexure of RGP lenses on the eye. Where a material is too flexible, corneal toricity can encourage bending of the lens upon insertion due to the capillary effects of the tears, and further bending during the blink due to the forces of the lids. Again, material design is of the utmost importance, and, according to recent work by Fatt (1988), is of greater importance than the modulus of elasticity of the material itself. The degree to which a fiat slab of material will distort is dependent upon the first power of the modulus,-but the third power of the thickness and the third power of the diameter. The modulus of elasticity varies only by a factor of two between the most flexible and the least flexible materials available on the market
today, and ~ difference can be easily accounted for by using a slightly thicker, slightly larger lens. As an example, an increase of about 17% in thickness (say, from 0.15 to 0.175 ram) and 8% in diameter (from 9.0 to 9.7 ram) produces a 100% increase in the 'stiffness' of a lens. Since we are principally concerned with negative power lenses which thicken toward the periphery, the increase in thickness and diameter may not even need be this big. The conclusion from Fart's work is that the modulus of elasticity is of minor concern as a property of RGP materials, and that lens design is the critical factor. Mechanical properties also become of great importance in the consideration of lens fabrication. Certain materials cannot be lathed, which places restrictions on lens designs, may increase the cost of manufacture, and means that all lenses must be delivered from the central place of production. Wettability . A major prerequisite of a material for use in contact lenses is the ability of the material to hold a stable tear layer. A surface which does not wet does not allow adequate refraction of light and so may decrease the wearer's vision, as well as allowing drying of the proteins on the surface which may lead to deposit formation. Many of the general concepts of wettability have previously been reviewed by Fatt (1984). A number of important points are borne out in his paper. Fatt stated that the concept of wettability has no real correlate in scientific terms. One may speak of a contact angle, which may be taken as a measure of hydrophilicity of a surface. A wet'table material will have a low contact angle, and a non-wettable surface will have a high contact angle. However, a variety of techniques exist for the measurement of contact angle (Sessile drop, Captive Bubble, Wilhelmy Plate), and the practitioner is confronted with many different values of contact angles for contact lens materials. It is often difficult to determine how a contact angle measurement has been achieved, which method produces clinically applicable results, and whether results from different investigators can be compared. A major difference exists in advancing angle versus receding angle measurements. When a drop of liquid is
Remove Liquid
Add Liquid
Advancing Angle Fig. 1, The contact angle 0 of a drop of liquid on a surface increases momentarily if more liquid is added, The shape of the drop reaches equilibrium with the liquid contacting the surface at an angle equal to the
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Receding Angle
advancing contact angle. Removal of some of the liquid decreases the angle of contact, and equilibrium is reached at a new contact angle, the receding angle.
Transaction5 BCLA tnu:rna6onat Cc,nference 1988
placed on the surface of a material, the angle that the edge of the drop makes with the surface, the contact angle, is determined by the interfacial tension. If a small amount of liquid is added to the drop, the angle will temporarily increase and the drop will spread until equilibrium is again reached, when the contact angle will be the same as for the smaller drop. This is known as the advancing angle. This concept is illustrated in Figure 1. If some of the liquid is now removed,, the contact angle will decrease and the area of the drop in contact with the surface will shrink until a new equilibrium is reached. However, it is noteworthy that the contact angle at equilibrium is now very much different to the advancing angle, this new angle is termed the receding angle, and it will usually be significantly lower than the advancing angle.
The portion of the surface of the material that was covered by the liquid has undergone a change in surface energy; it is essentially more hydrophilic. This phenomenon is known as hysteresis (Lambert et al, 1985), and will occur to different extents in different materials depending upon the chemical structure of the material. When a liquid is in contact with the surface the more hydrophilic groups are attracted to the surface, for example the hydroxyl groups in HEMA material in Fig 2. However, when air is in contact with the surface, the hydrophilic groups are attracted more towards the inside of the material, and hence, for HEMA, the more hydrophobic methyl groups are turned towards the surface. A material with a more rigid structure, such as PMMA will show less hysteresis, and consequently, less difference in advancing and receding angles. Currently popular RGP materials show considerable hysteresis, and consequently, will be more hydrophilic following storage in liquid media. The phenomenon justifies the practice of using wetting drops, and of the need to store RGP materials in liquid, whereas PMMA may be stored dry. It also stands to reason that where the tears consistently break over the front surface of a material in vivo, the hysteresis phenomenon will aggravate the problem by making the surface less 'wettable'. Despite the attention giving to contact angles, and th~ importance of material hysteresis, contact angles measured in vitro are of little use for the prediction of wetting performance in the eye. A chemical property of
a surface is that it must be in equilibrium with the medium which surrounds it. Even a 'clean' surface, when placed into a near vacuum will attract minute particles of dust from that atmosphere. So when a lens is placed in the eye, the surface will come into equilibrium with the tear fluid by a build up of tear constituents until the chemical potential of the particles in the tears equals the potential of those on the surface. As well as being an important factor in the build-up of lens deposits (see below), this means that the surface properties will change. The coated lens may have totally different wetting properties to the uncoated lens. Benjamin and co-workers (1986) has demonstrated this effect by measuring the contact angle of drops of saline placed onto lens whilst being worn by patients in the supine position. As expected, the contact angle changes dramatically following blinking by the patient, as the surface becomes coated with constituents from the tears. The coating serves to improve the wettability of the material. This .simple experiment demonstrates the futility on in vitro contact angle measurements for predicting in eye wettability of a lens. Clinically, the wettability of a contact lens is best judged by simple observation techniques, such as break-up time measurements with either the biomicroscope, keratometer or placido disc. Since the average blink rate may commonly fall as low as 5 per minute during periods of concentration, the break-up time should not be less than 12 seconds or the lens will not be completely wet. The characteristic of lens materials that makes them wettable is a negatively charged surface. In effect, the surface of all materials when placed in solution will take on a relative negative charge, and the degree of this charge is what will determine the extent of wetting. Incorporation of methacrylic acid into the polymer has been found to be successful for improving in vivo wetting performance. However, this serves to increase the attraction of lysozyme to the surface and other more suitable wetting agents need to be explored. Resistance to Surface Deposition One of the major difficulties for both patients and clinicians is accumulation of material from the tear layer on the lens surface. Surface deposits may affect vision and wetting, and provide a stimulus to an
AIR
~CH2-CH2\ CH2-CH2~ OH LENS OH Fig. 2. When the surface of a H E M A lens is in contact with air, the hydrophobic methyl groups of the chain are exposed at the surface. When the surface is in aqueous
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Conference
1988
CH2-CHJ CH 2-CH!OH LENS medium, the hydrophilic hydroxyl groups are oriented towards the surface. This phenomenon is known as hysteresis.
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immunological reaction. There is the potential for each of the tear constituents to adsorb to the surface of a contact lens, and proteins, lipids, glycoproteins, calcium and other environmental matter have been found in accumulations of deposit, the principal offender is protein, of which lysozyme, lactoferrin, albumin (tear specific), pre-albumin, PMFA, immunoglobin comprise the bulk. Adsorption of protein to a.material surface is a complicated matter. A great deal may be learnt from studies of the adsorption characteristics of biomaterials used for artificial vessels and valves. Whilst blood is significantly more complicated to study than tear fluid, containment of protein adsorption during contact lens wear presents the additional challenge of dealing with an air interface. A s detailed above, the potential of a particular species within solution must equal the potential of the species at the surface. Thus a certain amount of material deposition will always occur when a lens is covered by the tear film. Physical evidence of this aggregation has been observed with the electron microscope (Fowler and Allansmith, 1980). Where a species remains unchanged in its conformation u p o n adsorption, equilibrium will eventuate with minimal build-up on the surface. However, in some cases, the species will change in conformation upon adsorption and will not contribute to the chemical potential so far as the original species goes. This means that more of the species will be attracted to the surface, only to change in conformation and so the process will continue. The concept is illustrated in Fig 3. Further complications arise if the second and third layer which are laid down change in conformation in a different manner to the first layer. The use of attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) allows the deposited material to be identified and conformation of adsorbed proteins to be ascertained
(Castilto et al, 1984). Both lysozyme and albumin typically change from a predominantly 0~-helix conformation to a 13-sheet conformation on contact with the surface of a contact lens. A wide variety of factors influence the degree to which specific proteins WIUbe attracted to the surface of a material. In a number of cases, simplistic models of protein adsorption have been proposed. For example, methacrylic acid (MAA) is often incorporated into a material to increase the wettability. The inclusion of MAA contributes to an increase in the negative surface charge, which then attracts lysozyme, which is the only positively charged protein to be found in any quantity in the tears. Whilst the inclusion of MAA does increase the adsorption of lyso~me dramatically, there are many other factors aside from simple electrostatic attraction in the explanation of the increased surface build-up. The following list of forces and bonds which may occur during protein accumulation is a testimony of the complexity of the phenomenon (Absotom et al, 1984; Sharma, 1984): London dispersion forces, hydrogen bonds, dipole-dipole interaction, donor acceptor bonds, electrostatic interactions, acid-base bonds, biochemicals interactions (ligand-receptors), Van der Waals forces, Keesom forces, Debye-Falkenhagen forces. Given that a wide range of factors operate in the attraction and binding of proteins to a lens surface, relatively few specific properties of the lens material play a role. The charge of the surface is an important variable. All surfaces acquire a negative charge when placed in aqueous medium, but the extent of this charge will vary between materials. Pure silicone has little charge, and consequently, does not adsorb a great degree of protein. Furthermore, that protein which is attracted is relatively easy to move. More highly charged surfaces will bind protein tenaciously. It is of interest to note that less wet-table surfaces bind little protein,
®
®®
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®
®
® surface
Fig. 3. The molecules of species A in solution are at equilibrium with the molecules on the surface. If conformational changes occur to species A on contact
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iii iiiiiiiiii!iiiil
® ®
solution
® ® ® ® solution
surface
with the surface such that a new chemical entity is formed, species B, then more molecules of species A are attracted to the surface to attain equilibrium.
Transactions BCLA [ntc,"nationa! Conference 1988
whereas more highly charged, wettable surfaces suffer protein build-up. This scientific reasoning contrasts with the clinical observation and the known phenomenon of protein degradation upon drying. Material composition is another important variable. The basic constituents may have specific attraction for certain molecules, especially where these constituents are impurities not removed during the manufacturing process. In corporation of fluorine into a material has the effect of reducing protein aggregation. Furthermore inhomogeneity within a material can create regions with greater affinity to protein deposition. Surface irregularities contribute to adsorption presumably by increasing the surface area, and by providing sites which allow greater capacity for permanent binding.A recent laboratory study found that lathe cut lenses bind approximately twice as much protein as spun-cast lenses (Castillo et al, 1986). The accumulation of protein occurs selectively with competition between different components for binding sites. The charge on the protein is one aspect of the species which determines the composition of surface build-up. Lysozyme has a positive charge, and is thus attracted to the negative charge on a lens surface. Other characteristics of the protein species which influence accumulation include the molecular weight and size, and obviously the concentation of the species in the tears. Patient characteristics must also be involved in protein accumulation since some wearers can go for years without deposition, where others continually 'lay down' protein. Tear pH, osmolarity and temperature are some relevant variables. The ability of the tears to wet the lens surface is another likely contributing factor, drying contributing to greater protein degradation. Another consideration is the frequency and force of the blink, since agitation increases the amount of protein bound to the surface. The preceding discussion has focused on protein adsorption. Protein is also adsorbed, and the involvement of this protein in creating immunological stimuli is not certain. Lysozyme can enter the matrix of most soft lens materials, and apparently attaches to the chains without any obvious side-effects. Albumin is not absorbed into lower water content materials but will enter the matrix of higher water content materials, where the pore size is considerably larger. It is apparently for this reason that higher water content materials can not be thermally disinfected without suffering discoloration. Globulins are too large to enter most available hydrogels. Since protein adsorption can not be avoided, material optimisation needs to be based on developing a surface which will attract 'desirable' proteins with minimal conformational change. The corneal surface attracts mucin to the surface which makes the surface wettable without build-up of protein. A lens surface which attracts mucopolysaccharides in this way would obviously be a great advantage.
Transactions BCLA International Conference 1988
Options in Material Production From the drawing board to the final lens product, the material scientist has a wide range of factors which may be varied but must be controlled to produce the 'ideal' polymer. The choice of monomer to be polymerized and thus form the backbone of the material will determine a number of the material properties. Methyl methacrylate gives a material with great mechanical stability, but poor oxygen permeability. Silicone groups reduce the mechanical strength and the wettability but add to the oxygen permeability. Fluorine adds to the oxygen permeability and the wettability but may adversely effect the mechanical properties. Cross-linking agents need to be added to provide strength to the material. These will determine the hydration of hydrogel materials, and also influence the wettability. Wetting agents can also be added, but these need to be balanced against their protein adsorption capacity, and the other effects that they are likely to have. For instance, methacrylic acid is often added to increase" wettability, however, its presence strongly attracts build up of the tear protein, lysozyme. Between methods, the regularity of polymerization, retention of by-products and speed of reaction will vary. Radiation polymerization encourages homogeneity in the degree of polymerization throughout the material, although bulk polymerization is an easier process. The above v~/riations will produce materials with differing degrees of crystallinity. The method of lens fabrication will be varied depending upon the properties of the material. Although the majority of lenses are lathe cut, allowing greater flexibility in design, it may not be possible to cut the material in this way because of its physical properties. Cast or injection molding or spin casting may provide greater reproducibility or may simply be necessary because the material cannot be lathed. All of the factors mentioned so far will affect the final surface quality of a lens. In particular, the method of lens fabrication will have a significant effect on the properties of the surface. However, it is possible through a variety of techniques to add a surface coat to produce a variety of surface properties. These may be induced by both chemical and radiation means. Despite the ability to control the above variables in material production, there are a number of factors which remain uncontrollable. These include impurities in the bulk material, failure to totally eliminate the byproducts, the random nature of polymerization, and the viscosity, degree of agitation and heat transfer during the polymerization prodecure. These factors lead to variation in the material properties between batches of the same material. .Recently, there have been reports of surface treatments which reduce protein build-up. Oxygen plasma treatment improved both the wettability and protein resistance of a rigid gas permeable lens surface (Hough and Patel, 1986). Another chemical surface treatment has made the Hydrocurve 55 % water content material significantly more resistant TM
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to protein build-up without interfering with other material characteristics (Manrique, 1987). More widespread use of surface treatments should occur as new technology in surface chemistry is incorporated into contact lens manufacture. Discussion The recent court action in the United States which reduces the number of major manufacturers researching new lens materials may retard the development of new technology in contact lens material production. On the other hand, the restrictions on the use of current concepts may instigate research into new areas of material development. A review of patent applications, however, indicates that most of the recent apph'cations have been for materials based on fluorosiloxane acrylate materials, not dissimilar in basic sturcture to the Equalens which is currently being marketed. The current trend for increasing use of hard-gas permeable materials is expected to continue. Where the past few years have seen growth in the area of siloxane acrylate materials, the next few years will see increasing sales of materials containing fluorine. These materials have good oxygen permeability, good wettability and reasonable resistance from protein accumulation, but variable dimensional stability. The incorporation of methacrylic acid as a wetting agent in these materials means that lysozyme deposition is still a likely occurrence. •The pure fluoropolymer material produced by 3M and marketed by Allergan is likely to have a major impact on the industry over the coming years. It has high oxygen permeability, good wettability and freedom from protein build-up, the major disadvantage with the material is its poor machinability, which requires distribution from large central manufacturing centres and limitations to the range of parameters.
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As more sophisticated polymer technology is incorporated into contact lens development, we should see increasing use of surface treatments on base structures with more desirable mechanical properties and a high level of oxygen permeability. Soft lens materials which contain low amounts of water, but with high oxygen permeability is another exciting advance which should also be introduced at some time in the future. Meanwhile, lens fitters should continue to improve lens design to the extent that torics and bifocal contact lenses can be fitted with simplicity. References Absolom, DR, Zingg W, Van Oss CA,Neumann AW. (1984) Protein and platelet interactions with polymer surfaces. Biomat Med Dev Art Org 12: 235-266. Benjamin WJ, Yeager MD, Desai NN, Carmichael CA. (1986) In vivo analysis of contact angles. Int Eyecare 2: 163-170. Castillo EI, Koenig JL, Anderson JM, Kliment CK, Lo L (1984) Surface of analysis of biomedical polymers by attenuated total reflectance -- Fournier transform infrared. Biomaterials$: 186193. Castfllo EJ, Koenig JL, Anderson JM. (1986).Characteri/.ation of protein adsorption on soft contact lenses IV Comparison of in vivo spoilage with the in vitro adsorption of tear proteins. Biomaterials 7: 89-96. Fatt I. (1984) Prentice medal lecture. A m l Optom Physiol Opt61: 419-430. Fatt I. (1988) Personal communication. Fowler SA, Allansmith MR. (1980) The surface of continuously worn contact lenses Arch Ophthalmot98: 1233-1236. Hough DA, Patel KID. (1986) Case report. Plasma modification of GPH lenses -- an unexpected clinical result, l Brit Contact Lens Assoc 9: 38-40. Lambert DW, Sibley M, Dabezies OH. (1985) Wetting. In Contact Lenses. The CLAO Guide to Basic Science and Clinical Practice, ed Dabezies OH, pp 8.1-8.13. Manrique J. (1987) Hydrocurve Elite ~ ...The rendering of soft lenses soil resistant. Contemporary Optom 6: 9-13. Peppas NA, Yang W-H M. (1981) Properties-based optimisation of the structure of polymers for contact lens applications. Contact Intraoc Lens MealJ7: 300-313. Schwartz CA. (1988) Technology spurs gowth. Contact Lens Forum 13: 42-49. Sharma CP. (1984) Surface-interface energy contributions to blood compatibility. Biomat Med Dev Art Org 12: 197-213.
Transa.-'tions 8CLA International Cordcreac~ 1988