BIOCOMPATIBILITY

Biocompatibility and Silicone Hydrogels

A look at oxygen permeability, biofilm formation, lipid and protein deposition, and how they affect lens wear.

By Gina M. Wesley, OD, MS, FAAO

Dr. Wesley is located in the Twin Cities metro region of Minnesota, where she practices full-scope optometry with special interests in contact lenses, anterior segment disease, and children's eye care. Dr. Wesley currently publishes and lectures on various eyecare topics.

Of all the recent advancements in contact lens technology, silicone hydrogel contact lenses represent one of the most significant developments of the past 20 years. Answering the need for increased oxygen permeability, these lenses have changed the world's contact lens market. However, as any new technology surfaces, so do possible shortcomings as these lenses are worn and tested by the population at large. Clinical observations have drawn attention to issues such as corneal staining and solution incompatibility as well as inflammatory events.

These observations are the basis for many exploratory studies that examine factors such as oxygen permeability, biofilm formation, lipid and protein deposition, and underlying inflammation. This article will summarize recent findings regarding silicone hydrogel lenses and how, ultimately, this impacts daily clinical practices.

Silicone Hydrogels and the Ocular Surface

Silicone hydrogels have managed to combine the positive characteristics of traditional soft contact lenses with the superior solubility of oxygen in silicone. The limiting factor for oxygen flow in traditional soft contact lenses, or HEMA-based lenses (poly 2-hydroxyethyl methacrylate), is water content (Stapleton et al, 2006) These relatively hydrophilic lenses were met with thickness and comfort challenges when trying to increase water content, and thus, oxygen flow. Silicone hydrogels have solved this problem by utilizing the silicone material. This has largely reduced lens-induced hypoxia in contact lens wearers in general. Although hydrophobic by nature, manufacturers have enhanced the surface wettability of silicone hydrogels through surface treatments or by incorporating internal wetting agents (Stapleton et al, 2006; Staple-ton et al, 2002).

In any contact lens wearer, we must examine the effects of the lens on the corneal surface. The health of the cornea relies on its inherent ability to replace the epithelium and to repair damage. (Wolosin et al, 2001) The limbal epithelial stem cells are crucial for this self-renewal (Stapleton et al, 2006). Lens-induced hypoxia and mechanical trauma have been cited as possible causes of deficiency of these cells.

Although recent studies comparing silicone hy-drogel wear with no lens wear have found no clinically distinguishable difference in corneal homeostasis, inflammatory and infectious events involving the cornea still occur (Wolosin et al, 2001; Huang, 1989). This suggests other underlying causes.

The tear film plays a vital role in successful lens wear, perhaps more than ever with silicone hydrogels. Tear film stability is necessary for normal optical functioning, lubrication, and defense against pathogens and foreign debris. Lens wear can destabilize the tear film and its functions through mechanical interference and thinning of the lipid layer. This becomes important when examining the closed-eye environment (Sack et al, 1992; Sack et al, 1996; Willcox et al, 1997; Thakur, 1998). Tear-defense mechanisms are shown to stagnate and take on the qualities of subclinical inflammation when an eye is closed. This is intensified during contact lens wear.

Information is somewhat limited, but suggests that silicone hydrogel lenses have a similar negative impact on closed-eye tear defenses compared to traditional HEMA-based lenses (Stapleton et al, 2006). This hypothesis is essential to keep in mind as more extended and flexible-wear options are utilized with silicone hydrogel lens technology.

Biofilm Formation

Biofilms are collections of microorganisms encased in a matrix that is often comprised of both bacterial and host materials (Behlau et al, 2008). They frequently form on abiotic materials such as contact lenses and their storage cases. Biofilms form large microbial communities on the lens surface and have coordinated multi-cellular behavior, which can confound the medical and optical properties of the lens. Biofilms can prolong the retention time of organisms at the ocular surface because of their adhesion to the lens; as a result, pathogenicity of the organism may potentially increase (McLaughlin-Borlace et al, 2008).

There is growing evidence that bacterial biofilm formation plays a role in a range of ocular infections (McLaughlin-Borlace et al, 1998; Zegans, et al, 2002).

The exact role of biofilms in relation to contact lenses has been a focus of recent research. The cells within a biofilm have shown increased resistance to antimicrobial agents, which may be attributed to the simple “bulk” of the film itself. This bulk can physically exclude antimicrobials from contacting the offending pathogens (McLaughlin-Borlace et al, 1998). More recent evidence also suggests that resistance may be attributed to alterations in the bacterial cells themselves — phenotypic changes associated with an adherent existence, altering the hydrophobicity and cell wall structure (Boyd et al, 1995; Jones et al, 2003).

To add to the complex formation of biofilms, one must examine biofilms and their relationship to contact lens deposition. Lens wear causes changes in the structure of the tear film, particularly the lipid layer (Jenkinson, 1995). Silicone hydrogel lenses have differing chemistries compared to traditional HEMA-based lenses, and their hydrophobic surfaces deposit minimal amounts of protein and higher amounts of lipids (Lorentz, 2007). There have been early speculations that this may be significant in silicone hydrogel lens wearers (Ghormley, 2006) (Figures 1 and 2).

Figure 1. Protein film formation on soft lens surface.

Figure 2. Lipid and protein deposition on soft lens surface.

Due to increased lysozyme content, researchers theorize that protein deposits on HEMA-based lenses have increased antibiotic properties, discouraging biofilm formation on the contact lens itself (Szczot-ka-Flynn, 2009; Szczotka-Flynn, 2008). Lipid deposition, in contrast, does not have those antibiotic properties, and biofilm formation can thus flourish (Figure 3). Additionally, the closed eye environment has been shown to decrease the rates of what little lysozyme deposition develops on silicone hydrogels (Sack et al, 1996). Again, given the increased flexible and extended wear options of silicone hydrogel lenses, the closed eye environment, and increased lipid deposits, these advanced lenses need to be monitored closely to ensure appropriate cleaning and disinfection to avoid deposit-related complications.

Figure 3. Lipid caliculi on soft lens surface.

Biofilm presence and density are not necessarily related to poor hygiene compliance, either (McLaughlin-Borlace et al, 1998; Wilson et al, 1990; Stapleton et al, 1995). Multiple studies have shown no correlation of biofilms with poor observance of manufacturers' recommended instructions for cleaning and disinfection. This confirms that good hygiene practice does not automatically result in contamination-free lenses and storage cases. Ultimately, biofilms are demonstrating to be a potentially complex factor in ocular inflammatory and infectious events in contact lens wearers.

Inflammatory/Infectious Events and Possible Link to Biofilms

But is the disruption of the tear film and subsequent lipid deposition and/or biofilm formation linked to inflammatory or infectious events with silicone hydrogels? To further explore this, we can look at ocular surface inflammation in relation to silicone hydrogels.

Current studies have examined the incidence of corneal inflammatory events (CIE) with continuous wear in silicone hydrogels. A recent study, (Szczotka-Flynn et al, 2009) examined the predictive factors for corneal infiltrates in silicone hydrogel wearers. Because overnight lens wear has long been associated with an increased risk of infiltrate formation, this study set out to examine the incidence of infiltrates over a period of three years in lotrafilcon A (Night & Day, CIBA Vision) lenses. Researchers found that there were two main predictors of a CIE in continuous wear of the lotrafilcon A lens: corneal staining and limbal redness. Limbal redness increased the chance of CIE development three-fold, whereas corneal staining increased the chance of CIE development seven-fold (Stapleton, et al, 1995).

How does this compare to traditional, low-Dk HEMA-based lenses? In 2007, Stapleton et al examined the epidemiology of contact lens-related infiltrates. They, too, noted that increased corneal staining elevated the risk for a CIE in silicone hydro-gels. However, the risk for development of microbial keratitis was about the same when comparing hydrogels and silicone hydrogels.

This observation was supported in additional studies as well (Sczcotka-Flynn et al, 2007; Schein et al, 2005). Interestingly, bacterial contamination of the storage case and contact lenses showed increased risk for developing a CIE in both lens types, suggesting biofilm formation may play a role in inducing corneal inflammation (Stapleton et al, 2007). Although hypoxia-related risks have been diminished with the introduction of silicone hydrogels, issues of contamination and biofilms in both storage cases and of the lens itself may be a factor in inflammatory occurrences.

When examining CIE, recent evidence (Szczotka-Flynn, 2008) suggests that silicone hydrogels may pose a higher risk, especially if biofilm formation is detected. An additional study (Szczot-ka-Flynn, 2009) revealed that 67 percent of patients who had a CIE also had lens microbial contamination. Theoretically, increased oxygen flow in silicone hydrogels might decrease the likelihood of a CIE. However, these findings further support the idea that hypoxia is not the culprit in CIE formation for silicone hydrogel wearers. Possibly, biofilms, lens material, and their interaction with the ocular surface are playing a large part in inflammation.

When examining care systems, realizing the potential interaction they play in possible CIE formation is critical. Ongoing studies will help to continually define what combinations of newer silicone hydrogel lens materials and care solutions are potentially harmful to the ocular surface. Recent evidence shows that solution toxicity may increase the likelihood of CIEs threefold and that corneal staining is related to low grade ocular surface inflammation (Carnt et al, 2007) (Figure 4). Potential sources of this corneal staining/CIE formation have been linked in several major studies to solution preservative uptake and release into the pre-corneal tear film (Jones et al, 2002; Andrasko et al, 2007).

Figure 4. Solution-based toxicity.

Larger preservative molecules in multipurpose contact lens systems and/or utilizing dual disinfection to efficiently clean and disinfect lenses has shown better safety profiles for patient use (Andrasko et al 2007; Epstein, 2002). Hydrogen peroxide systems have also demonstrated low degrees of corneal toxicity (Andrasko et al, 2007). Additionally, minimizing care system interactions with the ocular surface via use of daily disposable lenses is an alternate method to avoid CIE formation. In any case, there is a call to continually develop solutions that have high degrees of disinfection, but low risk to ocular surface health.

In a series of recent articles, CIEs have been classified on a continuous spectrum of disease severity, possibly indicating a greater chance of morbidity (Sczcotka-Flynn et al, 2007; Chalmers et al, 2005). Even though they usually resolve completely and efficiently, the simple fact of their occurrence indicates a break-down in the ocular tissue integrity. Estimates of the total number of contact lens wearers worldwide are greater than 100 million (Stapleton et al, 2007).

Although CIEs occur relatively infrequently, their impact could still be staggering. The greater the knowledge base as to the etiology of CIEs and the association with silicone hydrogel lenses, the better outcomes in performance for patients and eye-care professionals.

Conclusion

Silicone hydrogels' role in today's contact lens practice is tremendous in terms of advancements. Although there are inflammatory and infectious events associated with increased use, silicone hydrogels still perform extremely well in terms of vast ocular physiological improvements.

While instances of CIEs related to silicone hydrogel use are relatively rare, it is still important to examine possible etiologies of these occurrences. Lipid deposition, ocular surface interaction and biofilms may certainly be a factor. To further improve bio-compatibility of silicone hydrogels with the ocular surface, we need a more thorough understanding of how the contact lens interacts with the cornea, lids, and tear film. Further studies should involve potential modifications of lens materials and their surface treatments to prevent adherence of deposits and biofilm colonization. There also exists, perhaps, an opportunity to develop contact lens care systems that improve the tear film stability as well as increase penetration of the disinfecting agents into biofilms.

Knowledge of the incidence and associated risk factors of contact lens complications will enable you to accurately inform patients on the risks of developing a CIE. In addition to the aforementioned studies, educating our patients on lens care compliance may help limit an inflammatory or infectious event. Ultimately, the information we continually gather as primary eyecare practitioners will assist in the understanding of the pathogenesis of contact lens-related eye disease. CLS

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