Article Date: 2/1/2006

EVOLUTION OF A REVOLUTION
Silicone Hydrogels: The Evolution of a Revolution
The ongoing story of the development and enhancement of high-Dk silicone hydrogel contact lenses.
By Deborah Sweeney, BOptom, PhD, FAAO, Desmond Fonn, DipOptom, MOptom, and Kylie Evans, BA

The development of highly oxygen-permeable silicone hydrogel lenses is the biggest breakthrough in lens material technology since soft lenses entered the market in the 1970s. Not only do silicone hydrogel materials provide ocular health benefits, they also allow people to wear contact lenses longer, making continuous wear a healthier option. This development should encourage many practitioners to consider silicone hydrogels for all contact lens patients.

Raising the Bar

In the 1950s, Otto Wichterle formulated the requirements for a material that would be compatible with living tissue. He sought to develop a material:

• With elasticity similar to that of the tissue with which it will come in contact

• Without extractive irritants

• That's permeable for water-
soluble, low molecular weight metabolites

• That's chemically and biochemically stable under physiological conditions.

At the Czechoslovak Academy of Sciences, Wichterle and Drashoslav Lim developed hydroxyethylmethacrylate (HEMA) and filed patents for many possible applications, including contact lenses. In fact, they used the first HEMA lenses on their own eyes in 1957. Wichterle and Lim persisted despite criticism from many skeptics, and they created a whole new industry and method of vision correction.

Continuous Wear

Primarily, patients want clear vision, comfort and safety, but they also want convenience. Silicone hydrogel contact lenses were developed to enable people to wear soft lenses for longer periods. In addition, practitioners want lenses that don't alter corneal physiology.

In the early 1980s, de Carle1 developed high water content hydrogel lenses for continuous wear. The U.S. Food and Drug Administration (FDA) approved his Permalens (71% water content) and other lenses for 2 weeks of extended wear in the early 1980s. Within a few years, the FDA approved these lenses for up to 30 days of continuous wear. By 1985, about 4 million people were extended lens wearers.

Although initial reports of continuous wear hydrogels were quite encouraging,1–5 Ruben6 was the first to report complications with continuous wear hydrogel lenses in 1977. Later Zantos 7 and Zantos and Holden 8 reported complication rates of over 35% with hydrogel continuous wear. The Göteborg study 9 of uniocular continuous wear showed significant reductions in epithelial thickness and oxygen uptake rate; incidence of epithelial microcysts, stromal thinning and chronic daytime edema; and increased endothelial polymegethism. Inflammatory adverse events affected a significant proportion of continuous-wear patients,10 but more importantly, serious infections with hydrogel continuous wear occurred. 11–15

Oxygen Is Key

Conventional hydrogel contact lenses reduce the
oxygen available to the cornea, and oxygen deprivation can cause ocular changes, even in the very short term.16,17 There is extensive evidence that low-Dk hydrogels cause these changes18,19 (Figure 1). Even in daily wear, corneal exhaustion syndrome can occur among long-term wearers of low-DK lenses.20

Figure 1: Evidence of hypoxia: a. corneal edema; b. limbal hyperemia; c. vascular response; d. epithelial microcysts; endothelial polymegethism.

Oxygen deprivation is of particular concern in the closed-eye state. The eye must obtain all its oxygen from under the lid, and tears contribute little or no oxygen.9 As noted by the Göteborg study and many others,22-30 changes induced by chronic hypoxia can be observed in all layers of the cornea in all long-term hydrogel extended wear and continuous wear patients.

Holden and Mertz Criteria

What level of oxygen does the eye need to be healthy? This was a controversial question for many years.

Polse and Mandell31 found that an atmospheric level of only 1.5% to 2.5% oxygen (11 to 19 mm Hg or 1.5 to 2.5 kPa) helped the eye avoid corneal edema. But later research raised this estimate to 3.5 to 5.5%,32 10%33 and even 15%.34

Holden and Mertz35 established that during overnight wear of lenses, the minimum Dk/t required to avoid lens-induced edema is 87 x 10-9 (cm x mL O2)/(s x mL x mm Hg). The no-lens level of swelling they used to derive the 87 value was 4%, from the work of Mertz,36 but others have estimated lower values, such as 3.2% by La Hood and colleagues37 and 2.33% by Fonn and colleagues.38

Harvitt and Bonanno39 support this with their mathematical model of oxygen diffusion across the cornea. They suggested that a Dk/t of 125 x 10-9 (cm x mL O2)/(s x mL x mm Hg) is needed to avoid stromal anoxia. The Papas model16 also estimates the level of peripheral Dk/t required to prevent limbal hyperemia is 125 x 10-9 (cm mL O2)(s mL mm Hg)-1. Smith and colleagues40 suggest at least 10% of the hypoxic stress of the average cornea remains with a lens Dk/t of 90 x 10-9 (cm x mL O2)/(s x mL x mm Hg). To halve this residual hypoxia would require an estimated Dk/t of at least 175 x 10-9 (cm x mL O2)/(s x mL x mm Hg).

High Water Content Hydrogels

In hydrogel lenses, the water content of the material provides oxygen to the cornea. Increasing the water content produces several limitations, including low modulus of elasticity and low tear strength. According to Friends and colleagues,41 researchers at Bausch & Lomb worked to formulate a high-strength, non-ionic hydrogel using novel strengthening agents. Although they produced variants that delivered comfort, deposit resistance, wettability and sufficient oxygen transmissibility for daily wear, evaporative corneal staining prevented thin designs from being used for extended wear.

In addition, the Dk of water (80 barrers) limits the maximum Dk that can be achieved with a conventional hydrogel lens material. (Note: A barrer is a unit of oxygen permeability. According to the American Standard ANSI Z80[1].20-1998, the unit for oxygen permeability (Dk) is: 10-11 (cm2/sec) x (mL[O2]/(mL x mm Hg); or equivalently 10-11 (cm3 [O2] x cm)/( cm2 x sec x mm Hg) equals 1 barrer.)

Even if a 100% water content lens were possible, this lens could never satisfy the Holden-Mertz criterion for continuous wear. The oxygen permeability of current hydrogel lens materials ranges from 20 to 40 barrers, and, on average, the lenses induce between 9% and 14% overnight corneal swelling.26,37,38

To make continuous wear possible, the contact lens industry needed an entirely new lens material — one that provides sufficient oxygen to enable people to wear lenses without inducing any more edema than the closed eye without a lens.

Silicone Elastomers

The first attempt to break free of the hydrogel mold was the silicone elastomer lens, first available in the 1970s. Silicone elastomer lenses had exceptional oxygen transmissibility because of the high solubility of oxygen in silicone. And overnight edema levels with these lenses were significantly less than those observed during eye closure without lens wear.42 However, problems with manufacturing resulted in poor edge shape and discomfort. The lenses also were prone to poor wettability and excessive lipid deposits.43,44 Because they contained no water, silicone elastomer lenses did not promote flow of fluid through the lens, and they tended to adhere to the cornea.44–46 Finally, the lenses caused adverse events, including ulcers.43,47–50

The industry worked to design low-water, lipid-resistant, transparent, wettable silicone-based materials. Although short-term evaluation of these materials suggested excellent wettability and lipid resistance, on-eye movement remained an unresolved issue.41 Researchers had not yet achieved the material they needed. The development of silicone hydrogels brought this goal within reach.

Silicone Hydrogel Lenses

Figure 2: Relationship between oxygen permeability (Dk) with equilibrium water content for conventional hydrogel and silicone hydrogel materials.

Silicone hydrogel is a revolutionary lens material because it incorporates the high Dk levels of silicone with the benefits of conventional hydrogel lens materials. This means that, unlike conventional hydrogels that limit the Dk to the water content, the Dk of silicone hydrogels is controlled by the level of silicone incorporated into the base material (Figure 2). The result is a far higher Dk. In addition, the hydrogel phase facilitates lens movement on the cornea because water and ions diffuse through the lens.

Combining conventional hydrogel monomers with silicone proved to be an enormous challenge, and it took considerable intellectual input and financial resources to create these materials. Indeed, the process has been compared to mixing oil and water, while maintaining optical clarity.51

Silicone hydrogel lenses provide up to eight times the oxygen transmissibility of conventional soft lenses while providing initial comfort, fitting performance and surface characteristics similar to conventional soft lenses. The only disadvantage of the first-generation silicone hydrogel materials is that they are hydrophobic, thus they need treatment to make them hydrophilic.

Perhaps the earliest patents for silicone hydrogel lenses went to those developed by Kyoichi Tanaka and others at the Toyo Contact Lens Company in 1979.52 Tanaka described a silicone hydrogel copolymer suitable for use in soft contact lenses, which had excellent oxygen permeability in spite of low water content and could be comfortably worn continuously for long periods without foreign-body sensation or pain. Another 20 years elapsed before the widespread launch of silicone hydrogel contact lenses, illustrating the complexity of the chemistry involved.53

Continuous-wear R and D

The development of the first silicone hydrogel contact lenses to be approved for 30-day continuous wear involved a worldwide collaboration between the Cooperative Research Centre for Eye Research and Technology (CRCERT), a multidisciplinary research and development organization in Sydney, Australia; Novartis AG, a life sciences company based in Switzerland; and CIBA Vision, the eye care unit of Novartis AG, with laboratories in Atlanta.

Clinical and biological scientists from CRCERT and the Cornea and Contact Lens Research Unit of the University of New South Wales set the performance goals. Material scientists, polymer chemists and surface scientists from all three collaborators determined the material needs and achieved the set targets; while clinical scientists verified the ocular performance. The three entities involved in research and development had joint ownership of the intellectual property.

Scientists were determined to push the frontiers of materials science. Their initial aim was to make a material of at least 90 barrers/cm, at a time when all available lenses had an oxygen transmissibility of less than 40 barrers/cm.

30-day Lenses Re-enter the Market

CIBA Vision launched Focus Night & Day lenses in 1999. These lenses are made from a fluorosiloxane hydrogel material (lotrafilcon A) with a water content of 24% and a Dk/t of 175 x 10-9 (cm x mL O2)/(s x mL x mm Hg) at –3.00D. Lotrafilcon A has a biphasic molecular structure, in which the siloxy phase facilitates the solubility and oxygen transmissibility and the hydrogel phase transmits water and oxygen. The phases work concurrently, allowing good lens movement and continuous transmission of oxygen and aqueous salts.

On Oct. 12, 2001, the FDA approved Focus Night & Day silicone hydrogel contact lenses for up to 30 nights of continuous wear. This was a milestone in the development of successful continuous-wear lenses. The lenses reached $1 million in U.S. sales faster than any contact lens in history.

Also in 1999, Bausch & Lomb brought PureVision (balafilcon A) lenses to market. They were the first daily-wear silicone hydrogel lenses, with a water content of 35% and a Dk/t of 110 x 10-9 (cm x mL O2)/(s x mL x mm Hg) at –3.00D. Balafilcon A is a homogeneous combination of the silicone-containing monomer polydimethylsiloxane (a vinyl carbamate derivative of TRIS), copolymerized with the hydrophilic hydrogel monomer N-vinyl pyrrolidone (NVP). In 2001, these lenses received FDA approval for continuous wear up to 30 nights.

The new, highly oxygen-permeable fluorosiloxane hydrogel materials eliminated physiological changes due to hypoxia. Overnight edema levels with the new-generation materials were similar to the levels seen with no lens wear,38,54 and other signs of hypoxia were eliminated.17,19,54–56

In a 2004 survey, contact lens practitioners in 14 countries indicated they prescribe silicone hydrogel lenses for the majority of continuous-wear fits (83%) in most countries, with the highest levels in Australia (96%), Canada (89%) and the United Kingdom (89%).58

Beyond Continuous Wear

As Night & Day and PureVision lenses made their way in the market, it became clear that these lenses offer more than just continuous wear. High oxygen transmissibility is important to daily wearers, including hyperopes, astigmats and presbyopes. Not only do the advantages benefit the increasing number of older contact lens wearers, but they also may be recommended for the ocular health of young people who may wear contact lenses for many decades.

CIBA Vision's O2Optix lenses were designed to bring the advantages of high oxygen transmissibility to a wider market by making the silicone hydrogel material more affordable and thus suitable for daily wear. CIBA Vision launched the lenses, based on the Night & Day technology, in the United States in September 2004 and in Australia in February 2005. O2Optix lenses are made of lotrafilcon B, which has high permeability and a higher water content than Night & Day, making the material softer.

Another important advance that improves comfort and helps reduce dryness involves leachable materials, using soluble polymers instead of hydrophilic coatings. Vistakon's Acuvue Advance material, galyfilcon A, contains an internal wetting agent based on polyvinyl pyrrolidone (PVP). Currently approved for daily wear, this first of the second-generation silicone hydrogels has an inversion marker and a UV blocker. Vistakon's Acuvue Oasys (senofilcon A), a new silicone hydrogel introduced in 2005, has a PVP-based internal wetting agent similar to Acuvue Advance, called Hydraclear Plus. It has about 30% more wetting agent than Acuvue Advance, which the manufacturer says makes the lens softer and more wettable.

The Story Continues

The development of high-Dk silicone hydrogel contact lenses with oxygen transmissibilities that far exceed the Holden-Mertz criterion for overnight wear is the greatest breakthrough in the contact lens industry in the last 30 years. These lenses are appropriate for daily wear, extended wear or continuous wear, with minimal long-term impact on corneal physiology. Thus they are an important step forward in providing the majority of patients with the comfort, flexibility and convenience they desire.

Of course, when seen in the context of more than 2 billion spectacle wearers, contact lenses are yet to really come of age. But this is not the end of the story. There are still patient and physiological needs to meet, and new designs for all vision corrections waiting to be developed. Silicone hydrogels — and the scientific and collaborative approaches that made them possible — will continue to provide the foundation of contact lens improvements into the future.

Dr. Sweeney is CEO of the Vision Cooperative Research Centre (CRC), Sydney, Australia, and professor at the University of New South Wales.

 

 

Dr. Fonn is director of the Centre for Contact Lens Research and professor at the School of Optometry, University of Waterloo, Waterloo, Ontario, Canada.

Ms. Evans is communications manager at the Vision CRC and the Institute for Eye Research, Sydney, Australia.

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Contact Lens Spectrum, Issue: February 2006