EVOLUTION OF A REVOLUTION
Hydrogels: The Evolution of a Revolution
ongoing story of the development and enhancement of high-Dk silicone hydrogel contact
By Deborah Sweeney, BOptom, PhD, FAAO, Desmond
Fonn, DipOptom, MOptom, and Kylie Evans, BA
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
With elasticity similar to that of
the tissue with which it will come in contact
Without extractive irritants
That's permeable for water-
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.
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
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.
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
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
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 Z80.20-1998, 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
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.
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
Silicone Hydrogel Lenses
Figure 2: Relationship between oxygen permeability
(Dk) with equilibrium water content for conventional hydrogel and silicone hydrogel
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
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.
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,
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