The Genesis of Silicone Hydrogels

The Genesis of Silicone Hydrogels

Dr. Jones: Let's begin by asking Professor Brien Holden, one of the acknowledged inventors of SiHy materials, about the major advantages that these materials bring to the modern contact lens practice. Brien, please chronicle for us the development of SiHy materials and tell us what you think are the major reasons practitioners should be fitting SiHy lenses as their first lens of choice.

Dr. Holden: Conventional hydrogel contact lens materials are associated with reduced oxygen availability, potentially resulting in short-, medium- or long-term hypoxic effects on the ocular surface, particularly if worn overnight. Of course, oxygen availability varies with lens thickness and water content.1,2 In a conventional hydrogel lens, water is the primary conduit for oxygen transmission. However, even a 100% pure water lens wouldn't have the necessary permeability to sustain normal corneal metabolism, and further, higher water content increases lens fragility and evaporative corneal staining, especially with thin lens designs.3

An early attempt at developing an intrinsically more permeable contact lens, using a silicone elastomeric material, had exceptional oxygen transmissibility due to the high solubility of oxygen in silicone. However, lens adherence, lack of wettability and edge manufacturing difficulties limited its utility and acceptance. The next step — the incorporation of silicone into a hydrogel lens material — was indeed a challenge. However, SiHy lenses were developed with novel chemistries and released just over 10 years ago (Focus Night & Day† from Ciba Vision and PureVision† from Bausch + Lomb).4-6 These lenses represented the first major breakthrough in soft lens technology since hydrogel lenses had been invented by Wichterle in the 1960s. Combining siloxane and hydrophilic phases in the right parameters provided more of the oxygen that the cornea and limbal stem cells need.7 It's worth mentioning that a critical factor in the success of SiHy lenses was that they incorporated a hydrophilic phase that facilitated lens movement, a discovery reported in the now-famous Nicolson patent.4

SiHys ushered in a new era, enabling wearers to use their contact lenses for long periods without the vascularization, striae, folds, polymegathism and refractive changes that were characteristic of conventional hydrogel contact lens hypoxia.7-9 In some patients, overnight edema levels could be as low as those seen with no lens wear.10

Dr. Jones: Thanks for setting the scene for us. Now, bearing in mind that these materials were developed more than 10 years ago, have things changed very much since they were released? Have we seen any issues with those early SiHy materials that needed addressing that are seen less with current lenses?

Dr. Holden: The earliest SiHy lenses contained high levels of siloxane that gave very high permeabilities, but also resulted in materials that were very stiff or had a high modulus of elasticity.11 This resulted in lenses that provided, in some cases, less than optimal initial comfort, and design issues that led to mechanical insult to the ocular surface and under the lid, resulting in mechanical complications such as superior epithelial arcuate lesions (SEALs)12,13 and contact lens-associated papillary conjunctivitis (CLPC).13,14

Dr. Jones: Brien, from what I understand, to overcome these issues, manufacturers developed materials with lower modulus values and redesigned the highmodulus materials to incorporate more sophisticated designs and offer an increased number of base curves. Did that effort reduce the number of mechanical complications?

Dr. Holden: Yes, that's correct. We've seen a reduction in those initial mechanical issues over time — now they're observed far less frequently.

Dr. Jones: Brien, most of the developments you've talked about so far relate to the bulk properties of the materials (oxygen transport and modulus). We know that initial attempts to incorporate silicone into hydrogel lenses failed due to issues associated with surface wettability, deposition and comfort. What did the manufacturers of modern SiHy materials do to overcome this?

Dr. Holden: You're correct, the incorporation of siloxanes and fluoroalkyls into SiHys created potential challenges related to the materials' hydrophobic and lipophilic nature. The first-generation SiHy materials overcame surface hydrophobicity by using various surface treatments6,11 and ongoing comfort was good after adaptation, especially in the troublesome environments where hydrogels caused dryness, such as air-conditioned rooms and aircraft cabins.15 The challenge for the surface chemists who were working for the contact lens companies that wanted to commercialize SiHy materials was to provide a contact lens material that performed well in any clinical setting, providing good comfort, low deposition and minimal bacterial adherence, while also satisfying the requirements of ease of manufacture and low cost. To render the contact lens surface more wettable, modification of the polymer surface was achieved using wet-chemical or plasma oxidation, and hydrolysis, as used in the Air Optix† Night & Day† (Ciba Vision) and PureVision† lenses (Bausch + Lomb).6,11 Later generations of SiHy lenses incorporated hydrophilic elements in the polymer and/or in the blister pack solution to increase initial comfort and obviate the need for surface treatment, as demonstrated by materials such as that used in Acuvue Oasys† (Vistakon) lenses.11,16

Dr. Jones: Brien, any final issues we should consider?

Dr. Holden: I feel one of the real disconnects with SiHys has been the lack of enhancement, and in some cases obvious incompatibility, of various care solutions with various SiHy products — even with lenses and care solutions coming from the same corporation.17-20 Certainly, no single care solution is ideal for every lens and every patient. Our IER Matrix studies19,21 detail the numbers of subjects who exhibit solution-induced corneal staining (SICS) after 3 months of using various combinations of SiHy materials and care solutions and can be used to get a better combination if your patients are having these problems. Our advice is that peroxide is associated with the lowest levels of corneal staining, infiltrates and discomfort in general, but even so, there are lenses that aren't best with peroxide for other aspects of performance. Likewise, differences between MPS formulations affect both lens-care solution compatibility and comfort.


Dr. Jones: Having set the scene with regard to the development of SiHy materials over the past decade, let's switch to another topic that's related to surface wettability: deposition. Historically, deposits with silicone elastomeric lenses were an issue, with many patients depositing on their contact lenses fairly quickly. So, what about SiHy lens materials? What do we know about deposition with these materials? I'll take the opportunity to address that, in light of Brien's excellent introduction to the historical development and advantages of modern SiHy materials.

As Brien pointed out, SiHy materials represent a family of materials whose properties are unlike any other previously developed for contact lens use. The incorporation of siloxane groups into the base hydrogel material has produced materials that have substantially improved oxygen transmission characteristics compared with conventional soft lens materials. Numerous clinical studies have demonstrated that the number of physiological complications induced by the wearing of such materials — on both a daily and an overnight wear basis — is significantly less than that seen with conventional materials.8,22-26 However, the migration of siloxane components to the material's surfaces results in relatively hydrophobic surfaces compared with conventional hydrogels and this results in a marked difference in the profile of deposition being observed on SiHy materials. This typically manifests itself clinically as lens surfaces that exhibit markedly increased deposition and reduced surface wettability (Figure 1).

Poorly wetting SiHy lens showing lens calculi (that are predominantly composed of lipid) and a poorly wetting surface shortly after a blink.

When it comes to deposition, it's worth discussing protein and lipid deposition, as their deposition profiles on conventional and SiHy materials are very different.

Much work has been undertaken on protein deposition. It's well established that conventional hydrogel materials, particularly those that are categorized as being high water, ionic (Group IV) materials such as etafilcon A, deposit large amounts of protein.27-30 However, much of this protein remains active or "native" and is relatively easily removed by merely soaking in a care solution overnight. This "passive" removal can be enhanced by the addition of chelating agents such as citrate or various surfactants into the formulation of the care solution used with the material.28,31 While ionic materials may deposit as much as 1000-1500μg of protein per lens (most of which is lysozyme),28,29 SiHy materials typically deposit <20μg/lens.27-29,32-37 However, studies28,30,32-33,38 have suggested that much of this protein is relatively deactivated or "denatured" and can be somewhat difficult to remove from SiHy materials. Two studies28,38 suggest that the degree of lysozyme denaturing could be impacted by both the composition of the care solution and the use of in-eye rewetting drops, with care solutions containing Tetronic 1304** exhibiting a reduction in the percentage of denatured lysozyme on the lens materials.

What about lipid deposition? Two clinical reports39,40 suggest that deposition with what appear to be lipids may be an issue with SiHy materials. Cheung and colleagues40 examined subjects who wore a SiHy lens in one eye and a hydrogel lens in the other and found that after 2 weeks, the SiHy material had more visible lipid deposits than the hydrogel material. Two laboratory-based studies41,42 and several clinical studies37,43-44 have quantified lipid deposits on SiHy materials, with most suggesting that values of 5-40μg/lens are typical and that values do appear to be similar or slightly higher on SiHy materials compared with hydrogel materials.

So, in conclusion it would appear that SiHy materials generally deposit lower levels of protein, much of which is relatively denatured. Although not as extensively studied, levels of lipid on SiHy lenses appear to be similar or slightly higher than that of conventional hydrogel materials and continue to be problematic for some, but not all, subjects.


Dr. Jones: Given that we have some understanding of the differences in deposition profile of SiHy materials versus conventional hydrogels and that issues relating to surface wettability may also arise, what benefits can we derive from the care solution, which obviously plays a critical role in contact lens wear? For this, let's turn to Art Epstein, OD.

Dr. Epstein: This is an area I've been interested in for quite some time. Historically, conventional polyHEMA-based hydrogel materials served well as the first soft lenses, but their limited oxygen transmissibility led to the development of the SiHy materials that dominate the market today.45,46 As with anything new, new materials and new care solutions may create new complexities. I think most practitioners would agree that "wetter is better" when it comes to keeping contact lens wearers comfortable. However, despite significant technological advances over the years, both conventional and SiHy materials continue to be plagued by comfort issues.47,48

Let's begin by considering SiHy materials. While great at transmitting oxygen, silicone is extremely hydrophobic, which makes silicone-based lenses even harder to keep wet than HEMA-based materials.49 The best explanation of the wetting challenge is that all lens materials contain a mix of hydrophilic and hydrophobic elements, which reorient during wear, with the hydrophilic ends seeking the water within the bulk of the lens and the hydrophobic ends aligning with the increasingly hydrophobic surface.50-53 Exposure of the lens surface to the atmosphere with each blink facilitates this reorientation (Figure 2).

Diagrammatic version of what happens at the surface of a contact lens when exposed to a hydrophobic environment. The hydrophilic sites orient themselves inwards towards the more "moist" environment, leaving a very hydrophobic surface.

Silicone hydrogels, because they contain a highly hydrophobic silicone species, can add additional hydrophobic sites to the lens surface, resulting in poor wetting. This is true even when the base material is surface treated or when moisture-retaining agents are added to the material to aid wettability. So, in a sense, SiHy lenses often start off at a wettability disadvantage.54 Surface treatments and moisture additives in the bulk material or blister pack may help, but they may lack "substantivity", which is the ability of such an agent to stick to a lens surface for prolonged periods, or in other words, to keep a lens wet, lubricated and moist for an entire wearing day.55

This is where advanced lens care solutions can add to the comfort equation. When appropriately formulated, lubricating or wetting agents within care solutions can have extremely long substantivity55 and help keep the lens surface lubricated, wet and comfortable for extended periods of time.

Dr. Jones: Art, modern care solutions often contain a number of lubricating and wetting agents. Can you tell us something about these products and provide your own personal clinical experience with them?

Dr. Epstein: The chemical aspects of contact lenses and care solutions intimidate some eyecare practitioners. But by looking at it from the surface chemistry perspective, it really helps us understand the potential clinical impact of the technology being used. Further, it can hopefully allow us to better meet our patient's needs. I discussed why we need lubricating and wetting agents just a moment ago. Put simply, it's because lens surfaces become less wet over the course of wear. That said, there appear to be two different schools of thought on how best to wet lens surfaces.54

The first approach relies on polysaccharide-based lubricating agents like carboxymethyl cellulose (CMC) and hydroxypropylmethyl cellulose (HPMC), the latter of which was used in Complete† MoisturePlus† (Abbott Medical Optics), which was recalled due to an association with Acanthamoeba keratitis.56,57 Another example is polyquaternium-10, which was used in ReNu† MoistureLoc† (Bausch + Lomb), which was recalled due to its association with fungal keratitis.57-59 More recently, another polysaccharide-based agent called hyaluronic acid is being utilized as a lubricating agent in a recently introduced, newly formulated care solution called Biotrue† (Bausch + Lomb).

The second approach consists of using surface-active, block copolymer agents such as Tetronic 1304** and C9ED3A (Figure 3) used in Opti-Free* Replenish* MPDS (Alcon), Tetronic 1107** used in various Bausch + Lomb care solutions, Poloxamer 237 used in Complete† MPS Easy Rub Formula (Abbott Medical Optics) and Pluronic 17R4† used in Clear Care† (Ciba Vision).54

The chemical structure of the TearGlyde* Reconditioning System (a combination of Tetronic 1304** and C9ED3A) used in Opti-Free* Replenish* MPDS (Alcon) to clean and wet hydrogel contact lenses.

Personal experience suggests that the polysaccharide-based lubricating agents are optimally effective as tear "bulking" agents rather than for lens surface wetting. Patients report improved initial comfort, but I don't find it's generally sustained over the course of the day. In contrast, block copolymer surface-active agents appear to produce comparatively prolonged surface moisture and, in my experience, enhanced and extended end of day comfort. In addition, block copolymers are synthetic molecules that can be specifically designed to better balance hydrophilic and hydrophobic sites, helping optimize moisture retention at the lens surface. This latitude allows the formulating scientist to be creative in optimizing clinical performance with modern lens materials that have a tendency to wet relatively poorly.60


Dr. Jones: Another issue of interest to clinicians regarding care solutions relates to the value of rubbing and/or rinsing the lenses. Because lipid and denatured protein are relatively difficult to remove from hydrophobic surfaces, would rubbing the lenses enhance deposit removal?

This is an interesting topic with relatively little data thus far published. Nichols39 examined two weekly replacement SiHy lenses and showed that adding a rub-and-rinse step significantly reduced visible deposition. Pucker36 examined the role of a rinsing step in aiding protein removal from a SiHy lens when used with "norub" care regimen. He showed that rinsing the SiHy contact lens after removal and prior to overnight disinfection removed approximately 50% of the protein associated with the lens on removal from the eye. However, recent work by Luensmann61 showed that lysozyme and albumin removal efficiency for a peroxide and an MPS product depended on the lens material and protein type investigated and that lens rubbing with MPS before soaking overnight did not significantly reduce the protein content on the lenses compared to non-rubbed lenses. Given the lack of data on this topic, particularly related to lipid deposition, it would appear that the jury is still out on this issue. However, some studies62, 63 show there are benefits to rubbing lenses. It would appear at the very least the lenses should be rinsed prior to an overnight soak in their solution.

Dr. Epstein: Lyndon, what do we know about the relative merits of lipid deposit removal between MPS systems and peroxide systems?

Dr. Jones: Once again, there's little published data and, to date, only two studies37,44 have investigated the impact of care solutions on SiHy lipid deposition. Zhao37 showed that lipid removal from certain SiHy materials was optimal for no-rub (rinse only) MPS systems, with cholesterol removal for the combinations of galyfilcon A (Acuvue Advance†)/Opti-Free Replenish MPS, senofilcon A (Acuvue Oasys†)/Aquify† and balafilcon A (PureVision†) with either of these two MPS care solutions being enhanced than when any of these SiHy materials were used with a rinse-only peroxide system. Heynen and colleagues44 quantified lipid deposition on senofilcon A (Acuvue Oasys†) SiHy lenses when disinfected with a rinse-only hydrogen peroxide system (Clear Care†) or a preserved MPS care solution using a 5-second rinse (Opti-Free Replenish MPS). They showed that the predominant lipids detected were cholesterol oleate and cholesterol and that use of the MPS care solution resulted in 36% less lipid deposition.44 Thus, published evidence would suggest that MPS care solutions compare favorably with peroxide systems in terms of removal of deposits from SiHy materials, but we do need more data.


Dr. Jones: While on the subject of care solutions, let's turn to an issue that has been the topic of much debate among researchers and clinicians: solution-induced corneal staining or SICS for short, which Brien mentioned earlier. Art, you were among an early group of clinicians involved in this debate, please share your thoughts.

Dr. Epstein: Lyndon, independently your group (at the Centre for Contact Lens Research at the University of Waterloo) and I were the first to report increased levels of corneal staining with a PHMB-based care solution and a SiHy lens (PureVision†, Bausch + Lomb).17,64-65 Several other researchers18,66-69 subsequently reported that certain combinations of SiHy lenses and care solutions resulted in this problem (Figure 4). Results of one investigator's series of studies investigating SICS can be seen at (Figure 5).70

Cornea exhibiting solution induced corneal staining after wearing a silicone hydrogel lens disinfected with a preserved multipurpose solution. Note the annular appearance of the staining and the sparing of the central cornea.

Results show percentage area of the cornea exhibiting corneal staining after two hours of lens wear using an acute exposure model.

SICS likely occurs secondary to uptake of the disinfectant and its subsequent release into the tear film and onto the ocular surface. Uptake of the biocide has been shown in several studies,71,72 including one performed by the U.S. FDA.73 Although it hasn't been discussed extensively in clinical circles, uptake of the biocide into the lens material may lead to loss of disinfecting effectiveness over time, by removing the antimicrobial from the care solution left in the lens case.71,74 Subsequently, high levels of disinfectants in the lens, released into the tear film when the lens is applied onto the eye, can be associated with high levels of corneal staining as the disinfectants are released.68,70,75-77

In my opinion, this has become more of an issue with SiHy lenses because some solution manufacturers haven't caught up with the rapid advances in lens material technology. Currently, there are only two care systems on the market that were FDA approved after the approval and introduction of most SiHy lenses, although more are expected in 2011. This is certainly something to look forward to as I hope we've learned a good deal in recent years regarding this issue.


Dr. Jones: Let's move away from the role of the care system and consider some potential complications. While SiHy materials have brought great advantages to clinicians and patients, they still have some issues that practitioners must address from time to time. Let's ask Dr. Szczotka-Flynn, who obtained her PhD investigating complications associated with the wear of SiHy materials, to discuss adverse events with SiHy lenses. Loretta, what are the most common adverse events that practitioners may encounter when fitting SiHy materials?

Dr. Szczotka-Flynn: SiHy lenses have been a long awaited, tremendous advancement in contact lens polymer technology. Compared to low Dk hydrogels, most hypoxic lens complications have been resolved. However, it has been well documented that other nonhypoxic lens-related complications remain or have increased. This is not unexpected, as the higher modulus of the SiHy lenses as a group would lead to the prediction of more mechanical complications. Indeed, as Brien discussed earlier, mechanical events, such as contact lens-induced papillary conjunctivitis and superior epithelial arcuate lesions, are more common in patients wearing SiHy lenses compared to low oxygen permeable lenses.14,78

Dr. Jones: SiHy materials were initially targeted at overnight wearers and several were approved for up to 30 nights of wear. Historically, we know conventional hydrogels were associated with an increased risk of developing microbial keratitis (MK) when worn overnight. Have SiHy materials had any impact on the numbers of patients developing MK?

Dr. Szczotka-Flynn: An unpredicted finding is that the rate of MK hasn't really changed during daily or overnight wear with SiHy lenses compared to low Dk hydrogel lenses.79,80 A large scale population-based epidemiological study80 in Australia reported that the rate of MK with SiHy lenses is 25.4 per 10,000 for extended wear, which is very similar to the rates reported in the 1980s and 1990s for low Dk lens wearers.81,82 Explanations for this unexpected finding include the speculation that hypoxia may not play as important a role in contact lens driven microbial invasion of the cornea as previously thought, or that these population-based studies are biased by early adopters of new technology.83 That is, perhaps the worst contact lens candidates have been put in the SiHy materials first, which raises the adverse event rate in this group as a whole.

Dr. Jones: Another issue of interest to practitioners relates to the development of various inflammatory complications such as sterile infiltrates, which are much more common than MK. How do rates of inflammatory events compare between SiHy and conventional materials?

Dr. Szczotka-Flynn: Well, another unpredicted finding is that the incidence of corneal inflammatory events (Figure 6) during extended wear with SiHy lenses is approximately twice that seen during extended wear with low Dk lenses.84,85 Bacterial bioburden on lens surfaces may drive these inflammatory events (especially during extended wear),86 but it's still unknown why SiHy lenses have an increased incidence of infiltrates. About 50% of all worn soft lenses, regardless of material, are found to harbor microorganisms, which is almost exclusively bacteria.87 The bacteria isolated are mostly considered normal flora, and the presence of ocular pathogens is typically sporadic and unpredictable. Thus, increased bacterial presence on SiHy lenses doesn't seem to be a likely explanation for the increased inflammatory events seen with SiHy lenses. Perhaps what we're visualizing is the normal response of the ocular surface to thwart bacterial invasion of the cornea. The improved physiological profile of the cornea beneath a SiHy lens may allow for more rapid activation of the immune response against bacterial ligands frequently present on all lens surfaces.

Residual corneal scar from a contact lens peripheral ulcer.

Dr. Jones: The issue of biofilms is a fascinating one. Loretta, can you share with us more information on biofilms? What exactly is a biofilm and what role do you think biofilm plays in the development of complications? Also, is there a difference in biofilm formation between SiHy and conventional hydrogels?

Dr. Szczotka-Flynn: Consistent with my thoughts above, there doesn't seem to be a large differential in the ability to form biofilm across and between SiHy lenses and low Dk lenses. Biofilms are mature complexes of carbohydrates, living and dead microorganisms that form on many biomedical devices, including contact lenses. Both bacterial and fungal contact lens- and lens case-associated biofilms have been studied at length in vitro. Once a microorganism converts to the biofilm form, they become highly resistant to disinfectants and the host immune response. In vivo studies of contact lens-associated biofilms are sparse, but they've shown that biofilm-coated lenses can be recovered from patients with severe forms of MK.88,89 Therefore, it's important to remove or prevent biofilm formation, regardless of lens type or mode of wear, from lens surfaces and lens cases. Some studies90,91 have shown that Polyquad* and Aldox*-preserved MPS care solutions and hydrogen peroxide-based systems are more efficacious against bacterial biofilms compared to other MPS care solutions (Figure 7).

Activity of contact lens cleaning solutions against P. aeruginosa, S. marcescens, or S. aureus grown as biofilms on lotrafilcon A lenses. The effect of contact lens care solutions against mature biofilm was assessed after soaking the biofilm coated lens in each manufacturer's solution for the recommended soak time. Data represent Mean ± Standard Deviation, for at least three replicates. Improved efficacy against biofilms would be displayed as lower bars in the graph compared to the untreated control.

Dr. Jones: In closing this topic, would you like to share with us what role you think rub and rinse plays in modifying the biofilm on the lens?

Dr. Szczotka-Flynn: Reducing the bioburden may be an important step in reducing microbial and infiltrative keratitis. Both rub and no-rub care solutions require a rinse step to reduce the bacterial load independently of the disinfecting capability of a product. Although it hasn't been tested, I suspect that rubbing might be more effective than rinsing alone in removal of biofilm complexes.


Dr. Jones: Well, that brings to a close our discussion about the current situation with SiHy materials. There's no doubt that these revolutionary materials have transformed contact lens practice and have pretty much eliminated hypoxic complications. However, there are still some issues that practitioners need to consider when using them. Studies have clearly shown that the deposition profile of SiHy and conventional materials vary dramatically and as patients transition from one material to another they may exhibit some deposition issues. If that should happen, the patient may benefit from introducing a rub-rinse step, using a surfactant-containing multipurpose system, paying attention to lid hygiene if they exhibit meibomian gland dysfunction or blepharitis, or replacing their lenses more frequently.

Does anyone have any key take-away points they'd like to share?

Dr. Holden: First, take care when choosing the care solution you prescribe when dispensing SiHy lenses. My second piece of advice is to use SiHy torics wherever possible, particularly for all patients with −0.75D cyls and above, as they are now quite reliable. Correcting even small cyls makes a big difference to the patient, especially for monovision wearers.

Dr. Epstein: I think the most important thing to keep in mind is that contact lenses are medical devices that bear some risk and that there's no magic lens or care solution that works 100% of the time for every patient. As discussed, SiHys have been tremendously beneficial, although we need to be mindful of issues that have surfaced since their introduction. Microbial keratitis rates haven't changed substantially with their introduction79,80,92 and corneal infiltrates are more common with SiHy materials,84,85 particularly with the extended wear modality, than with conventional hydrogels. That said, their benefits are still substantial but they still need to be fitted and monitored by an astute clinician who keeps lens care solution choice in mind.

Dr. Szczotka-Flynn: SiHy lenses represent a substantial improvement in contact lens technology. They are the lenses of the present and the future. Although they may be associated with more mechanically based adverse responses, these clinical findings aren't serious and can be easily managed. There are very few reasons to revert back and fit low Dk hydrogel lenses. Practitioners should continue to select patients for SiHy lens wear, and I am confident that future generations of SiHy lenses will decrease the incidence of adverse responses.

Dr. Jones: My thanks to each of you for your fascinating commentary on the current position with SiHy materials. Over the past decade, we've learned a great deal about these materials and your experience in dealing with various issues will be valuable to our readers. Finally, my thanks to Alcon for providing the funding to put this special supplement together.

*Registered trademark of Alcon
†Trademarks are the property of their respective owners.
**Tetronic is a registered trademark of BASF Corp.


1. Holden BA, Mertz GW. Critical oxygen levels to avoid corneal edema for daily and extended wear contact lenses. Invest Ophthalmol Vis Sci 1984;25:1161-1167.
2. Holden BA, Sweeney DF, Sanderson G. The minimum precorneal oxygen tension to avoid corneal edema. Invest Ophthalmol Vis Sci 1984;25:476-480.
3. Orsborn GN, Zantos SG. Corneal desiccation staining with thin high water content contact lenses. CLAO J 1988;14:81-85.
4. Nicolson P, Baron R, Chabrecek P, et al. Extended wear ophthalmic lens. CIBA Vision; CSIRO 1998;Patent number 5,760,100.
5. Nicolson PC, Vogt J. Soft contact lens polymers: an evolution. Biomaterials 2001;22:3273-3283.
6. Nicolson PC. Continuous wear contact lens surface chemistry and wearability. Eye Contact Lens 2003;29;1 Suppl:S30-S32,discussion S57-S59, S192-S194.
7. Stapleton F, Stretton S, Papas E, Skotnitsky C, Sweeney DF. Silicone hydrogel contact lenses and the ocular surface. Ocul Surf 2006;4:24-43.
8. Covey M, Sweeney DF, Terry R, Sankaridurg PR, Holden BA. Hypoxic effects on the anterior eye of high-Dk soft contact lens wearers are negligible. Optom Vis Sci 2001;78;2:95-99.
9. Sweeney DF. Clinical signs of hypoxia with high-Dk soft lens extended wear: is the cornea convinced? Eye Contact Lens 2003;29:S22-S25.
10. Fonn D, Bruce AS. A review of the Holden-Mertz criteria for critical oxygen transmission. Eye Contact Lens 2005;31:247-251.
11. Tighe B. Silicone hydrogels: Structure, properties and behaviour. In: Sweeney D, ed. Silicone Hydrogels: Continuous Wear Contact Lenses. Oxford: Butterworth-Heinemann. 2004:1-27.
12. Holden BA, Stephenson A, Stretton S, et al. Superior epithelial arcuate lesions with soft contact lens wear. Optom Vis Sci 2001;78:9-12.
13. Dumbleton K. Adverse events with silicone hydrogel continuous wear. Cont Lens Anterior Eye 2002;25:137-146.
14. Skotnitsky C, Sankaridurg PR, Sweeney DF, Holden BA. General and local contact lens induced papillary conjunctivitis (CLPC). Clin Exp Optom 2002;85:193-197.
15. Young G, Riley CM, Chalmers RL, Hunt C. Hydrogel lens comfort in challenging environments and the effect of refitting with silicone hydrogel lenses. Optom Vis Sci 2007;84:302-308.
16. Tighe B. Contact Lens Materials. In: Phillips A and Speedwell L, Editors, Contact Lenses. Edinburgh: Butterworth-Heinemann. 2006: 59-78.
17. Jones L, MacDougall N, Sorbara LG. Asymptomatic corneal staining associated with the use of balafilcon silicone-hydrogel contact lenses disinfected with a polyaminopropyl biguanide-preserved care regimen. Optom Vis Sci 2002;79:753-761.
18. Carnt N, Jalbert I, Stretton S, Naduvilath T, Papas E. Solution toxicity in soft contact lens daily wear is associated with corneal inflammation. Optom Vis Sci 2007;84:309-315.
19. Carnt N, Evans V, Holden B, et al. IER matrix update: adding another silicone hydrogel. Contact Lens Spectrum; March 2008; pp 28-35.
20. Carnt NA, Evans VE, Naduvilath TJ, et al. Contact lens-related adverse events and the silicone hydrogel lenses and daily wear care system used. Arch Ophthalmol 2009;127:1616-1623.
21. Carnt N, Willcox M, Evans V, et al. Corneal staining: The IER matrix study. Contact Lens Spectrum; September 2007; pp 38-43.
22. Papas EB, Vajdic CM, Austen R, Holden BA. High-oxygen-transmissibility soft contact lenses do not induce limbal hyperaemia. Curr Eye Res 1997;16:942-948.
23. Fonn D, MacDonald KE, Richter D, Pritchard N. The ocular response to extended wear of a high Dk silicone hydrogel contact lens. Clin Exp Optom 2002;85:176-182.
24. Jalbert I, Stretton S, Naduvilath T, Holden B, Keay L, Sweeney D. Changes in myopia with low-Dk hydrogel and high-Dk silicone hydrogel extended wear. Optom Vis Sci 2004;81:591-596.
25. Dumbleton KA, Chalmers RL, Richter DB, Fonn D. Vascular response to extended wear of hydrogel lenses with high and low oxygen permeability. Optom Vis Sci 2001;78:147-151.
26. Keay L, Sweeney DF, Jalbert I, Skotnitsky C, Holden BA. Microcyst response to high Dk/t silicone hydrogel contact lenses. Optom Vis Sci 2000;77:582-585.
27. Jones L, Senchyna M, Glasier MA, et al. Lysozyme and lipid deposition on silicone hydrogel contact lens materials. Eye Contact Lens 2003;29:S75-S79, discussion S83-S84, S192-S194.
28. Senchyna M, Jones L, Louie D, May C, Forbes I, Glasier MA. Quantitative and conformational characterization of lysozyme deposited on balafilcon and etafilcon contact lens materials. Curr Eye Res 2004;28:25-36.
29. Subbaraman LN, Glasier MA, Senchyna M, Sheardown H, Jones L. Kinetics of in vitro lysozyme deposition on silicone hydrogel, PMMA, and FDA groups I, II, and IV contact lens materials. Curr Eye Res 2006;31:787-796.
30. Subbaraman LN, Glasier MA, Senchyna M, Sheardown H, Jones L. Extraction efficiency of an extraction buffer used to quantify lysozyme deposition on conventional and silicone hydrogel contact lens materials. Eye Contact Lens 2007;33:169-173.
31. Hong B, Bilbaut T, Chowhan M, et al. Cleaning capability of citrate-containing vs. non-citrate contact lens cleaning solutions: an in vitro comparative study. Int Contact Lens Clin 1994;21:237-240.
32. Suwala M, Glasier MA, Subbaraman LN, Jones L. Quantity and conformation of lysozyme deposited on conventional and silicone hydrogel contact lens materials using an in vitro model. Eye Contact Lens 2007;33:138-143.
33. Boone A, Heynen M, Joyce E, Varikooty J, Jones L. Ex vivo protein deposition on bi-weekly silicone hydrogel contact lenses. Optom Vis Sci 2009;86:1241-1249.
34. Emch AJ, Nichols JJ. Proteins identified from care solution extractions of silicone hydrogels. Optom Vis Sci 2009;86:E123-131.
35. Green-Church KB, Nichols JJ. Mass spectrometry-based proteomic analyses of contact lens deposition. Mol Vis 2008;14:291-297.
36. Pucker AD, Nichols JJ. Impact of a rinse step on protein removal from silicone hydrogel contact lenses. Optom Vis Sci 2009;86:943-947.
37. Zhao Z, Carnt NA, Aliwarga Y, et al. Care regimen and lens material influence on silicone hydrogel contact lens deposition. Optom Vis Sci 2009;86:251-259.
38. Subbaraman LN, Bayer S, Glasier MA, Lorentz H, Senchyna M, Jones L. Rewetting drops containing surface active agents improve the clinical performance of silicone hydrogel contact lenses. Optom Vis Sci 2006;83:143-151.
39. Nichols JJ. Deposition rates and lens care influence on galyfilcon A silicone hydrogel lenses. Optom Vis Sci 2006;83:751-757.
40. Cheung SW, Cho P, Chan B, Choy C, Ng V. A comparative study of biweekly disposable contact lenses: silicone hydrogel versus hydrogel. Clin Exp Optom 2007;90:124-31.
41. Carney FP, Nash WL, Sentell KB. The adsorption of major tear film lipids in vitro to various silicone hydrogels over time. Invest Ophthalmol Vis Sci 2008;49:120-124.
42. Iwata M, Ohno S, Kawai T, Ichijima H, Cavanagh HD. In vitro evaluation of lipids adsorbed on silicone hydrogel contact lenses using a new gas chromatography/mass spectrometry analytical method. Eye Contact Lens 2008;34:272-280.
43. Maziarz EP, Stachowski MJ, Liu XM. Lipid deposition on silicone hydrogel lenses, part I: quantification of oleic acid, oleic acid methyl ester, and cholesterol. Eye Contact Lens 2006;32:300-307.
44. Heynen M, Lorentz H, Dumbleton K, et al. Lipid deposition on senofilcon A silicone hydrogel contact lenses disinfected with 1-step hydrogen peroxide and Polyquad(r)/Aldox(r)-preserved care regimens. ARVO abstract #5660/D969; from 2009 annual meeting.
45. Morgan PB, Woods C, Tranoudis I, et al. International contact lens prescribing in 2009. Contact Lens Spectrum; February 2010;p30.
46. Keay L, Edwards K, Stapleton F. An early assessment of silicone hydrogel safety: pearls and pitfalls, and current status. Eye Contact Lens 2007;33:358-61.
47. Begley CG, Caffery B, Nichols KK, Chalmers R. Responses of contact lens wearers to a dry eye survey. Optom Vis Sci 2000;77:40-46.
48. Epstein A. Contact lens dropout. Review of Contact Lenses. July 2003 p28.
49. Martin R, Sanchez I, de la Rosa C, et al. Differences in the daily symptoms associated with the silicone hydrogel contact lens wear. Eye Contact Lens 2010;36:49-53.
50. Penn LS, Miller B. A study of the primary cause of contact angle hysteresis on some polymeric solids. J Colloid Interface Sci 1980;78:238-241.
51. Yasuda H, Sharma A. Effect of orientation and mobility of polymer molecules at surfaces on contact angle and its hysteresis. J Polym Sci Polym Phys Ed 1981;19:285-291.
52. Birdi KS. Contact angle hysteresis on some polymeric solids. J Colloid Interface Sci 1982;88:290-293.
53. Maldonado-Codina C, Morgan PB. In vitro water wettability of silicone hydrogel contact lenses determined using the sessile drop and captive bubble techniques. J Biomed Mater Res A 2007;83:496-502.
54. Ketelson HA, Meadows DL, Stone RP. Dynamic wettability properties of a soft contact lens hydrogel. Colloids Surf B Biointerfaces 2005;40:1-9.
55. Meadows D, Ketelson H, McQueen N, et al. Dynamic wetting behaviour of pHEMA-MAA and silicone hydrogel contact lenses. Invest Ophthalmol Vis Sci 2004; ARVO abstract #1553.
56. Joslin CE, Tu EY, Shoff ME, et al. The association of contact lens solution use and Acanthamoeba keratitis. Am J Ophthalmol 2007;144:169-180.
57. Patel A, Hammersmith K. Contact lens-related microbial keratitis: recent outbreaks. Curr Opin Ophthalmol 2008;19:302-306.
58. Chang DC, Grant GB, O'Donnell K, et al. Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution. JAMA 2006;296:953-963.
59. Zhang S, Ahearn DG, Noble-Wang JA, et al. Growth and survival of Fusarium solani-F. oxysporum complex on stressed multipurpose contact lens care solution films on plastic surfaces in situ and in vitro. Cornea 2006;25:1210-1216.
60. Ketelson HA, Meadows DL, McQueen N, et al. Enhancing wettability with multi-purpose solutions. Review of Cornea and Contact Lenses; Jan/Feb 2005; pp 44-47.
61. Luensmann D, Heynen M, Liu L, Sheardown H, Jones L. The efficiency of contact lens care regimens on protein removal from hydrogel and silicone hydrogel lenses. Mol Vis 2010;16:79-92.
62. Shih K, Hu J, Sibley MJ. The microbiological benefit of cleaning and rinsing contact lenses. Int Contact Lens Clin 1985;12:235-242.
63. Butcko V, McMahon TT, Joslin CE, Jones L. Microbial keratitis and the role of rub and rinsing. Eye Contact Lens 2007;33:421-425.
64. Epstein A. SPK with daily wear of silicone hydrogel lenses and MPS. Contact Lens Spectrum; November 2002;p30.
65. Epstein A, Stone R. Understanding and managing risk in contact lens wear. Contact Lens Spectrum; March 2009;Special Supplement.
66. Garofalo RJ, Dassanayake N, Carey C, Stein J, Stone R, David R. Corneal staining and subjective symptoms with multipurpose solutions as a function of time. Eye Contact Lens 2005;31:166-174.
67. Dumbleton K, Keir N, Moezzi A, Feng Y, Jones L, Fonn D. Objective and subjective responses in patients refitted to daily-wear silicone hydrogel contact lenses. Optom Vis Sci 2006;83:758-68.
68. Andrasko G, Ryen K. A series of evaluations of MPS and silicone hydrogel lens combinations. Rev Cornea and Contact Lenses; March 2007;pp36-42.
69. Zigler L, Cedrone R, Evans D, Helbert-Green C, Shah T. Clinical evaluation of silicone hydrogel lens wear with a new multipurpose disinfection care product. Eye Contact Lens 2007;33:236-243.
70. Andrasko Corneal Staining Grid. Available at:; last accessed September 13, 2010.
71. Rosenthal RA, Dassanayake NL, Schlitzer RL, Schlech BA, Meadows DL, Stone RP. Biocide uptake in contact lenses and loss of fungicidal activity during storage of contact lenses. Eye Contact Lens 2006;32:262-266.
72. Powell CH, Lally JM, Hoong LD, Huth SW. Lipophilic versus hydrodynamic modes of uptake and release by contact lenses of active entities used in multipurpose solutions. Cont Lens Anterior Eye 2010;33:9-18.
73. Warburton K, Noble-Wang J, Henry B, et al. Absorption of alexidine by contact lenses and lens cases and its efects on disinfection efficacy against Fusarium solani. Poster presented during the annual meeting of the American Society for Microbiology; May 2007.
74. Dannelly HK, Waworuntu RV. Effectiveness of contact lens disinfectants after lens storage. Eye Contact Lens 2004;30:163-165.
75. Andrasko G, Ryen K, Garofalo RJ, et al. Compatibility of silicone hydrogel lenses with multi-purpose solutions. Invest Ophthalmol Vis Sci 2006; ARVO abstracts;E-abstract 2392.
76. Andrasko G. Solution-induced staining and comfort during lens wear. Contact Lens Spectrum; September 2008;pp 33-35.
77. Andrasko G, Ryen K. Corneal staining and comfort observed with traditional and silicone hydrogel lenses and multipurpose solution combinations. Optometry 2008;79:444-454.
78. Jalbert I, Sweeney DF, Holden BA. Epithelial split associated with wear of a silicone hydrogel contact lens. CLAO J 2001;27:231-233.
79. Dart JK, Radford CF, Minassian D, Verma S, Stapleton F. Risk factors for microbial keratitis with contemporary contact lenses: a case-control study. Ophthalmology 2008;115:1647-1654.
80. Stapleton F, Keay L, Edwards K, et al. The incidence of contact lens-related microbial keratitis in Australia. Ophthalmology 2008;115:1655-1662.
81. Poggio EC, Glynn RJ, Schein OD, et al. The incidence of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. N Engl J Med 1989;321:779-783.
82. Cheng KH, Leung SL, Hoekman HW, et al. Incidence of contact-lens-associated microbial keratitis and its related morbidity. Lancet 1999;354:181-185.
83. Keay L, Stapleton F, Schein O. Epidemiology of contact lens-related inflammation and microbial keratitis: a 20-year perspective. Eye Contact Lens 2007;33:346-353;discussion 362-363.
84. Radford CF, Minassian D, Dart JK, Stapleton F, Verma S. Risk factors for nonulcerative contact lens complications in an ophthalmic accident and emergency department: a case-control study. Ophthalmology 2009;116:385-392.
85. Szczotka-Flynn L, Diaz M. Risk of corneal inflammatory events with silicone hydrogel and low dk hydrogel extended contact lens wear: a meta-analysis. Optom Vis Sci 2007;84:247-256.
86. Szczotka-Flynn L, Lass JH, Sethi AK, et al. Risk factors for corneal infiltrative events during continuous wear of silicone hydrogel contact lenses. Invest Ophthalmol Vis Sci June 2010; Epub ahead of print.
87. Szczotka-Flynn LB, Pearlman E, Ghannoum M. Microbial contamination of contact lenses, lens care solutions, and their accessories: a literature review. Eye Contact Lens 2010;36:116-129.
88. Stapleton F, Dart J. Pseudomonas keratitis associated with biofilm formation on a disposable soft contact lens. Br J Ophthalmol 1995;79:864-865.
89. McLaughlin-Borlace L, Stapleton F, Matheson M, Dart JK. Bacterial biofilm on contact lenses and lens storage cases in wearers with microbial keratitis. J Appl Microbiol 1998;84:827-838.
90. Szczotka-Flynn LB, Imamura Y, Chandra J, et al. Increased resistance of contact lens-related bacterial biofilms to antimicrobial activity of soft contact lens care solutions. Cornea 2009;28:918-926.
91. Vermeltfoort PB, Hooymans JM, Busscher HJ, et al. Bacterial transmission from lens storage cases to contact lenses-Effects of lens care solutions and silver impregnation of cases. J Biomed Mater Res B Appl Biomater 2008;87:237-243.
92. Schein OD, McNally JJ, Katz J, et al. The incidence of microbial keratitis among wearers of a 30-day silicone hydrogel extended-wear contact lens. Ophthalmology 2005;112:2172-2179.
93. Epstein A, Stone R. Surface and polymer chemistry: The quest for comfort. Review of Cornea and Contact Lenses; Jan/Feb 2010;pp 15-19.