High technology contact lens materials and their biomimetic properties (C8636)

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The concept of using a material that sits directly on the cornea for optical correction dates back to Leonardo da Vinci in 1508. The first realisation did not come until almost 400 years later, in the form of a glass contact lens. Feinbloom took this to a more practical level in 1936, through the synthesis of a durable plastic hard lens, made of poly methyl methacrylate (PMMA).

This was followed 23 years later by Wichterle and Lim’s invention of the first ‘soft’ contact lens material, poly hydroxyl ethyl methacrylate (pHEMA). This material was a breakthrough and is the first of many refinements and new developments in hydrogel materials for contact lenses, which have been driven primarily by considerations of the safety and comfort of wearers.

The property of hydrogels which make them so suitable for the in vivo application of a vision correction device is the ability to swell and retain water. However, the material, once fashioned in a contact lens of a certain dioptre, must have flexible properties such that it will deform under the force of the eyelid during blinking, yet regain its original shape and position on the cornea.

This review will deal with two of the newest developments in contact lens materials. The first is the development of a suitable hydrogel material through which oxygen can permeate, thereby enabling the lens to be worn safely overnight. The second is the concept that the lens during the waking hours can be made more lubricious, and more comfortable, by the addition of suitable compounds during or directly post manufacture.

Chemistry of polyhema lenses

Before examining the newer developments in contact lens materials, the chemistry behind polyHEMA – and how this has been manipulated over the years – must be reviewed. HEMA lenses are made using polymers consisting of water-swollen networks (40-90 per cent water) based on hydrophilic monomers (Figure 1). These polymers have a long backbone from which a variety of chemical groups may be suspended. Such groups attract and bind water within the structure. Brian Tighe makes the analogy to a ‘washing line’ on which clothes are hung out to dry and explains that stability is achieved by crosslinking the washing lines.1 Of course, unlike clothes, these structures do not dry out. Without water, hydrogels become hard, glassy materials.

As shown in Figure 2, polyHEMA (pHEMA) is formed from a reaction between the HEMA monomer and a HEMA dimer (EGDM), by means of a catalyst. The monomers and dimers join up to form a large network. The original material developed by Wichterle and Lim was made purely from HEMA monomers, and once polymerised, had a water content of 38 per cent.

However, over time, contact lens manufacturers have introduced other functional groups into polyHEMA by a process of co-polymerisation. Two types of co-polymerisation are most often employed in the manufacture of contact lenses; the addition of hydrophobic (water-hating) monomers, yielding lower water content lenses, or the addition of hydrophilic (water-liking) monomers yielding higher water content lenses.

Oxygen and the cornea

In principle, the cornea is a ‘transparent skin’, essentially consisting of three layers of living tissue: the epithelium, the stroma and the endothelium. It is the epithelium, with its high turnover, that requires oxygen to sustain metabolism. Since there are no blood vessels in the cornea, most of the oxygen needed comes from the atmosphere in the open eye condition. When the eyes are closed, oxygen is provided mainly from capillary blood vessels in the conjunctiva, with some contribution from the aqueous humour in the anterior chamber.

Once a soft contact lens is placed over the cornea, the direct pathway for oxygen to reach the corneal epithelium is essentially blocked. During the day, when the eye is open, some oxygen can permeate a conventional hydrogel material from the atmosphere, with a small contribution coming from tear exchange. However, at night, when the eye is closed, insufficient amounts of oxygen permeate the lens to meet the metabolic demands of the cornea. This lack of oxygen (hypoxia) eventually affects all layers of the cornea, causing a dramatic change in metabolism. The net result of this is a significant swelling of the cornea and the neovascularisation of the cornea and conjunctiva, as the body strives to compensate for the oxygen deficiency state of the cornea.

A number of investigators have attempted to determine the minimal oxygen requirement for a healthy cornea. Holden and Mertz determined that an oxygen transmissibility of 87 Dk/t (x 10-9cm ml O2/sec ml mm Hg) was sufficient, based on corneal swelling measurements.2 This figure has been revised upwards to 125 Dk/t by Harvitt and Bonanno, using more comprehensive measurements of corneal hypoxia.3 Although the universal unit chosen to represent oxygen transmissibility, Dk/t, will vary with the thickness of the lens, it is assumed that the measurement refers to O2 transmissibility at the centre of the lens, the thinnest part.

The development of successful silicone hydrogels for contact lens materials

The first attempts to increase the oxygen transmissibility of a contact lens revolved around simple measures, such as increasing its water content and/or creating ultrathin lenses. Water, by itself, has an O2 partial pressure of 80 barrers, enough to sustain the life of a fully adapted creature such as a fish. However, it is not possible to rely on water content to transfer this amount of oxygen in a solid, flexible material containing components other than water. Nor is it possible to make a lens sufficiently thin to compensate for this, without significant handling problems.

Attention was drawn to highly oxygen permeable materials and compounds which have been used in other medical device applications, such as silicones and per fluorinated compounds.4 However, such materials, by themselves, were not suitable for contact lens wear, due to the fact that they were not able to move on the eye. The industry was forced to strive for a radical innovation, and a new family of materials was born, the silicone hydrogels. This family of materials have upheld their potential, namely as being able to produce highly oxygen transmissible soft lenses, which move on the eye, and display the comfort of a conventional hydrogel. This result would not have been achieved without clever chemistry and an understanding of basic physical chemistry properties of materials, allowing their manipulation.

The approach taken consisted mainly of preparing macro-monomers (partial building blocks) made up of silicone precursors (for example, PDMS) and hydrophilic monomers in various arrangements, joined sequentially, or branched (Figure 3). At the end of each macro-monomer branch, there is a polymerisable group joined to the last hydrophilic monomer to allow co-polymerisation of the macro-monomers.

If one measured a physio-chemical property of the macro-monomer by a technique such as differential scanning calorimetry (DSC), it would become clear that such macro-monomer building blocks actually display a two-phase morphology. This is because the hydrophobic (water repelling) nature of the PDMS precursors forces the hydrophilic portions to attempt to physically associate with each other. This can be seen as two distinct inflexion points in the DSC scan (Figure 4).

Therefore it was necessary to strive for an arrangement of blocks in the macro-monomer such that once polymerised, these two phases would become co-continuous. This is vital to allow the permeation of oxygen (silicone phase) right through the lens, while also allowing the transport of water and ions (hydrophilic units) from one side to the other. The latter is absolutely necessary to give the lens sufficient movement and therefore comfort on eye. An example of how this works is the simple sponge. The sponge contains ‘holes’ which fill up with water, but the holes do not penetrate all the way through the material. Yet, the material contains hydrophilic blocks in a continuous network, which can allow the water to pass all the way through even though the material is solid.

In chemical terms, this type of material is said to contain amphiphilic (both hydrophobic and hydrophilic) networks. This is based on the concept of ‘smart networks’, developed by Jewrajki et al.5 Such amphiphilic co-networks swell, both in water and organic solvents, and respond to changes in the environmental medium by morphological isomerisation. If this is considered in terms of the hydrophobic (PDMS) and hydrophilic blocks in the macro-monomers, it can be imagined that upon polymerisation, the immediate micro-environment of each type of block will change. If the chemistry is right (size, shape and self-bonding potential of each type of block), the phases will become co-continuous, because this will be the thermodynamically most favoured state.

Properties of silicone hydrogels

Each of the silicone hydrogel materials on the market today has its unique chemical constituents and arrangements, leading to differences in water content (24-47 per cent) and oxygen permeability (Table 1). In the latter category, Night and Day is the highest (140 Dk/t) and Acuvue Advance the lowest (60 Dk/t).

Once the basic problems of how to make such blended materials that would transport both oxygen and water/ions had been solved, it was necessary to consider how such materials would perform on the eye. The modulus and resulting stiffness of the lens had to considered, as well as making the surface properties compatible with the eye.

Modulus is a material property, whereas stiffness depends on the design and thickness of the lens profile. Since high plus and minus dioptre lenses have thick areas, they will automatically be stiffer. The lowest modulus material is Acuvue Advance (0.5 MPa), the highest is Night and Day (1.5 MPa). Although there appears to be a ‘trade-off’ between different material properties, it should be emphasised that all the lenses on the market today have successfully juggled this.

Materials containing silicones notoriously repel water and therefore cannot be used on the eye unless the surface of the resulting lens is modified. Again, modification of the surface has been treated differently by each manufacturer of silicone hydrogel lenses (Table 1). Techniques range from plasma deposition or oxidation, to adsorbing hydrophilic polymers, to building the desirable surface property into the bulk material chemistry. Under the atomic force microscope, these different treatments look remarkably different, yet each allows sufficient wetting of the lens for the designed wearing time. Their relationship to comfort and the formation of deposits is still under intensive investigation.6

Biomimesis

The term ‘biomimesis’ indicates the construction of artificial biomaterials that mimic natural forms and effects. It rests on the hypothesis that evolution has identified, over time, optimal solutions and that living beings have reached functional perfection which can be studied and imitated. The goal is to reintegrate the technosphere into the biosphere. A key route to biomimesis in contact lenses is an understanding of the cornea’s ability to maintain its surface, specifically in terms of levels of moisture and lubricity, and being able to replicate this on the front surface of a contact lens, throughout the wearing period of the lens. All contact lenses without this modification dry out between the blink (~ 6 seconds), whereas the surface of the cornea stays moist for 20-25 seconds.

The challenge of maintaining moisture and lubricity on the front surface of a contact lens is currently only being tackled in the daily disposable category. Daily disposable lenses have a much lower incidence of microbial keratitis, and are considered to be the safest wear modality. Since a fresh lens is inserted every morning, additive chemistry only has to work to maintain moisture and lubricity until the end of the day. Once this property has been successfully achieved in daily disposable lenses, these findings can be extended to further wear categories.

References

1. Bowers RW and Tighe BJ. Studies of the ocular compatibility of hydrogels. A review of the clinical manifestations of spoilation. Biomaterials, 1987; 8(3): 83-88.
2. Holden BA and Mertz GW. Critical oxygen levels to avoid corneal edema for daily and extended wear contact lenses. Invest Ophthalmol Vis Sci, 1984; 25(10): 1161-1167.
3. Harvitt DM and Bonanno JA. Re-evaluation of the oxygen diffusion model for predicting minimum contact lens Dk/t values needed to avoid corneal anoxia. Optom Vis Sci, 1999; 76(10): 712-719.
4. Clark LC Jr and Gollan F. Survival of mammals breathing organic liquid equilibrated with oxygen at atmospheric pressure. Science, 1966; 152(730): 1755-1756.
5. Jewrajka SK, Erdodi G, et al. Novel biostable and biocompatible amphiphilic membranes. J Biomed Mater Res A, 2007 Dec 17 (Epub ahead of print).
6. Dumbleton K, Keir N et al. Objective and subjective responses in patients refitted to daily-wear silicone hydrogel contact lenses. Optom Vis Sci, 2006; 83(10): 758-768.

? This article summarises a lecture entitled ‘High technology contact lens materials and their biomimetic properties’, delivered as part of the Symposium series on Advanced Materials, their Safety and Comfort, sponsored by CIBA Vision EMEA. The Symposia were held in eight cities throughout Europe over a two week period in the autumn of 2007.

The lecture on chemistry and properties of newly developed hydrogels was prepared and delivered by Dr Juergen Vogt (formerly head of R&D, CIBA Vision Corporation, currently PolyPhysConsult, Switzerland), and Professor Carol Morris, (formerly Distinguished Research Scientist at CIBA Vision Corporation, currently at Southern Cross University in Australia). The lecture has been transcribed for Optician by Professor Carol Morris.