Article

Soft Contact Lenses and (Dis)comfort

A look at where we’ve been and where we’re headed in terms of materials.

SOFT LENS COMFORT

Soft Contact Lenses and (Dis)comfort

A look at where we’ve been and where we’re headed in terms of materials.

By Tannin A. Schmidt, PhD, PEng

Hydrogel contact lenses first became available more than 30 years ago, providing significant improvements in overall lens comfort at the time. Silicone hydrogel lenses, with their improved oxygen and ionic permeability, were first marketed in the late 1990s; second- and third-generation lenses followed, moving away from surface modification and TRIS-based macromers, respectively (Jacob, 2013). Today, soft lenses dominate the market, comprising approximately 90% of 140 million lens wearers worldwide (Nichols, 2014). Despite the improvements in the silicone hydrogel lenses, which make up the majority of soft lenses in most markets, 12% to 51% of lens wearers still drop out (Nichols, Willcox et al, 2013). Despite significant research and development into lens polymers, design, replacement modalities, and care regimens/solutions over the past several decades, contact lens discomfort is still a pervasive clinical challenge in terms of prevention and management (Tighe, 2013).

Defining “contact lens discomfort” is not a simple task in itself, let alone identifying soft lens material properties and/or characteristics that cause or associate with contact lens discomfort. These were some of the motivating tasks of the recent Tear Film and Ocular Surface (TFOS) Society International Workshop on Contact Lens Discomfort (Nichols, Jones et al, 2013). This international consensus-building workshop—tasked with defining contact lens discomfort and evaluating it through an evidence-based approach—resulted in reports from eight topical subcommittees.

The consensus definition of contact lens discomfort was provided as “a condition characterized by episodic or persistent adverse ocular sensations related to lens wear, either with or without visual disturbance, resulting from reduced compatibility between the contact lens and the ocular environment, which can lead to decreasing wearing time and discontinuation of contact lens wear.” The workshop indicated two major categories of contact lens discomfort: contact lens (comprised of material, design, fit and wear, and lens care) and environment (inherent patient factors, modifiable patient factors, ocular environment, and external environment).

The purpose of this article is to provide an evidence-based review of soft contact lens materials, in general, as well as contemporary/newer characteristics associated with soft lens materials. Given the magnitude and extensiveness of the recently completed TFOS workshop, this review will first highlight relevant findings related to soft contact lens materials/properties, briefly address lens design and care solutions (Jones et al, 2013), discuss recent and selected characteristics since the completion of the workshop, and finish with a perspective on future challenges and opportunities.

Material Properties and Characteristics

Material properties and characteristics that have been studied in an attempt to elucidate their influence on, or association with, contact lens discomfort can be classified into bulk and surface. Bulk material properties include water content and ionicity, oxygen transmissibility, and modulus and mechanical factors. Surface material properties include wettability, wetting agent incorporation, and friction or lubrication.

Water Content and Ionicity Several studies indicate that low equilibrium water content is associated with increased comfort in traditional hydrogel lenses, with no direct impact of ionicity (Efron et al, 1986; Nichols and Sinnott, 2006; Young, 1996). Most silicone hydrogel materials have a low equilibrium water content, and one study demonstrated that five different silicone hydrogel materials performed similarly (Dumbleton et al, 2008), but also significantly differed in other material properties (oxygen transmissibility, modulus, and wettability), making it difficult to draw conclusions on the effect of these properties on contact lens comfort. To date, no studies have definitively been able to demonstrate a direct impact of water content and ionicity on contact lens discomfort for silicone hydrogels.

Oxygen Transmissibility Oxygen transmissibility was the motivating factor for silicone hydrogel contact lens development, and it is tempting to attribute measured increases in comfort with silicone hydrogels to this property. Unfortunately, it is not that simple. Indeed, some circumstantial evidence and clinical dogma suggest a role. However, while studies (Jones et al, 2013) have demonstrated that lenses with higher oxygen transmissibility are more comfortable compared to those with lower oxygen transmissibility, they also contain experimental design issues that inhibit us from being able to directly attribute this effect to oxygen transmissibility. No properly conducted, well-designed, randomized, controlled trial studies currently exist that can directly answer the question of whether oxygen transmissibility influences comfort.

Modulus From a bulk mechanical point of view, tensile modulus (or stiffness) is most often referenced for soft material lenses (for example: Horst et al, 2012; Jones et al, 2006; Tranoudis and Efron, 2004), which in itself can be influenced by other contact lens properties. Although first-generation silicone hydrogel lenses had higher tensile moduli compared to most traditional hydrogels, later-generation lenses have been developed with lower-modulus materials. In the few studies that used low-modulus hydrogel lenses as an appropriate control group to minimize bias, no differences in comfort were observed—or could be attributed to modulus—between traditional hydrogel and silicone hydrogel lenses (Cheung et al, 2007; Fonn and Dumbleton, 2003).

Wettability Wettability classically refers to the ability of a liquid to spread over a solid surface (e.g., tear fluid over a lens). Unfortunately, no physical measurement currently exists (in vitro, ex vivo, or in vivo) that can completely quantify wettability of lens materials. As such, no direct link exists between clinical measures of wettability—let alone laboratory measurements—and contact lens comfort; however, these measurements may be related to, or indicative of, the (fluid film) lubrication of lenses during wear as discussed below.

Wetting Agents Wetting agents can be incorporated into, and be releasable from, contact lens materials in an effort to improve comfort. Polyvinyl alcohol (PVA) incorporated into nelfilcon A material was suggested to contribute to its comfort through slow release (of residual entangled PVA) or through blink activation (Mahomed et al, 2004) from within the lens matrix (Maissa et al, 1998). Hyaluronic acid is a hydrophilic glycosaminoglycan found throughout the body that has a variety of biophysical attributes including, but not limited to, lubrication and hygroscopic properties. While it has been used as a novel internal wetting agent (Ali and Byrne, 2009; Weeks et al, 2012; Weeks et al, 2013), and recently in a multipurpose solution, no clinical studies have directly demonstrated improved contact lens comfort due to hyaluronan incorporation.

Friction The friction coefficient of lenses appears to be the one lens material property that is directly associated with contact lens discomfort, though to date it is only presented in studies that are conference proceedings (Brennan and Coles-Brennan, 2009; Coles-Brennan and Brennan, 2012; Kern et al, 2013). Friction coefficients are measured in vitro as a horizontal friction force divided by a normal force, and they provide an indication of the quality or extent of lubrication, or lubricity. Friction is a quantity and lubricity is a quality. Collectively, these studies have demonstrated a correlation between various in vitro friction measurements (Roba et al, 2011; Ross et al, 2005; Tucker et al, 2012) and end-of-day comfort, two-hour mean comfort, and application comfort. Currently, no peer-reviewed studies or publications, appropriately controlled or not, exist that demonstrate these relationships. Nevertheless, not surprisingly given these data, in vitro measurement of contact lens friction coefficients is an active area of research of great interest (Fonn, 2013; Osborn Lorenz, 2014), both academically and industrially, and is certainly an area of great opportunity to make progress in both understanding and resolving contact lens discomfort.

Design, Deposits, and Wear

While contact lens design is clearly important, there is very little consensus on the influence of various design attributes on contact lens discomfort. The lens edge (size, shape, and contour) does seem to be a critical design feature of soft contact lens materials that impacts comfort (Maissa et al, 2012; Young et al, 1993). Based on classic clinical observations that contact lens deposits from wear can impact lens performance (Doughman et al, 1975; Lowther and Hilbert, 1975), you would surmise that lens deposits indeed affect contact lens (dis)comfort. However, no relationship between contact lens deposits has been established, whether using visible methods to determine lens deposits or quantitative methods for protein, lipid, or mucin deposits. Conversely, protein deposit activity (or quality) could be related (Subbaraman et al, 2012), although further studies are required.

While it seems intuitive that increasing lens replacement frequency is likely best for ocular health, it is difficult to identify an optimum schedule. In addition, no definitive studies exist that further clarify this issue. Indeed, comparing the comfort of daily, flexible, extended, and continuous wear lenses is difficult due to various confounding factors.

Studies do exist that support the notion that lenses worn on a two-week schedule are more comfortable compared to those worn for a month (Jones et al, 1999; Long et al, 2009). Yet, there is also evidence indicating the opposite—that monthly lenses provide a modest, but statistically significant, improvement in comfort compared to two-week lenses (Dumbleton et al, 2010). Daily disposable silicone hydrogels have not been widely examined in terms of potential comfort advantage, although one study has reported end-of-day comfort and dryness ratings were significantly improved for daily disposable wear compared to the same material and design used in a reusable manner (Lazon de la Jara et al, 2013).

The effect of replacement frequency may be a confounding factor related to the impact of duration of wear on comfort. Nevertheless, there do not appear to be any well-conducted, well-designed, randomized controlled trials demonstrating that duration of wear is an important determinant for contact lens (dis)comfort. In summary, nearly all studies to date suggesting that frequent replacement schedules result in improved comfort do so on the basis of circumstantial evidence.

Lens Care Solutions

While it seems obvious that regular and thorough contact lens care will result in more comfortable contact lens wear, identifying specific potential formulations or components that directly affect contact lens (dis)comfort remains a challenge. For example, some studies indicate that use of a care solution with a specific biocide results in improved comfort compared to another product, yet there are too many components within a solution to attribute these findings to a single component (Begley et al, 1994; Corbin et al, 2010; Keir et al, 2010). Furthermore, different lenses may interact differently with various multipurpose solutions, resulting in varying amounts and types of components being adsorbed onto the surface, or into the bulk, of lens materials. Indeed, a recent study demonstrated that subjective satisfaction in symptomatic wearers can be influenced by the combination of a specific contact lens and care solution prescribed (Tilia et al, 2013).

Wetting agents and/or surfactants that are able to remain on the lens material have also been shown to improve subjective comfort (Thai et al, 2002; Yang et al, 2012), although the long-term efficacy of such agents warrants further investigation. Increased viscosity of lens care solutions may also contribute to comfort through a thicker, longer-lasting fluid layer (Nichols et al, 2005; Thai et al, 2002), possibly contributing to enhanced fluid film lubrication. Although, wetting agents with too high of a viscosity could result in blurring effects.

Newer/Contemporary Characteristics

Newer or contemporary characteristics related to soft lens materials exist in all three of the categories discussed above, and individually or collectively (eventually) may contribute to improved comfort for contact lens wearers.

The notion of viscosity-enhancing reagents is still an area of interest for lens care solutions. The viscosity of a solution and/or ability of water to sit on the surface of the contact lens could be contributing to enhanced comfort through improved fluid film lubrication of the lens.

In addition, the friction coefficient of lenses continues to be an area of great interest. Recently, another natural lubricant present on the eye, although not a viscous agent, lubricin (Schmidt et al, 2013), has been demonstrated to reduce friction of silicone hydrogels when articulated against human ocular tissues (Samsom et al, 2014). Additionally, studies from conference abstracts have evaluated the friction of worn—simulated (Tosatti et al, 2013) or real (Mann et al, 2013)—lenses and demonstrated that this can change, which suggests a potential mechanism relating friction to end-of-day dryness.

However, another recent study examined whether end-of-day contact lens discomfort is associated with short-term changes occurring to the lens itself. Interestingly, this study demonstrated that final comfort was in fact not influenced by replacing lenses midway through the wearing period, indicating that the decrease in comfort experienced by daily contact lens users is not caused by changes of the lens and suggesting that alternating factors such as fatigue or changes to other ocular tissues may be involved (Papas et al, 2014). Collectively, novel daily disposable lens materials coupled with the emergence of (natural) lubricating macromolecules, either in multipurpose solutions or wetting agents, and the association of contact lens friction to in vivo comfort provides the basis for exciting continued research.

Future Outlook and a Bioengineer’s Perspective

Future clinical trials and studies will benefit from employing the definition of contact lens discomfort as developed by the TFOS workshop, which will contribute to consistency across research efforts from both academia and industry. Most clinical trials to date have focused on, or been motivated by, the performance of a specific lens type (or solution/drop), which is certainly understandable given the number of clinical trials that are industry sponsored. However, future efforts that allow for the isolation of one (lens material/characteristic) factor will also contribute to further mechanistic understanding of contact lens (dis)comfort.

Of particular interest, as outlined by the workshop, will be elucidating whether the magnitude and timing of changes in lens materials/characteristics will relate to the magnitude/timing of contact lens discomfort. Collaborative efforts between academia and industry, in which the motivation of basic understanding and marketing/sales can perhaps be balanced, will be important for future progress.

Lastly, symptoms themselves as an outcome measurement will continue to be appropriate, as they are what relates to patient experiences and incites treatment, with the hope that basic researchers will be able to continue to develop materials with specific properties/characteristics that actually result in improved comfort for lens wearers.

Specifically, in vitro friction properties of contact lenses significantly correlating to in vivo comfort provides both opportunities and challenges for future studies. The opportunity is clear: If materials with improved lubrication, or decreased frictional properties, can be developed, then perhaps comfortable wearing time can be increased within a day and even over a lifetime.

The challenge is that the in vitro friction coefficient of contact lenses is not an absolute property of the lens, it is a systems property. Each test system can have advantages and disadvantages based on the rationale for, or purpose of, the study. Plainly put, friction coefficients of lenses depend on how they are measured (test geometry, loads, velocity—all of which contribute to the mode of lubrication), on what (synthetic test surfaces versus native tissues), and in what (test lubricants).

In an ideal world, while absolute magnitude of measured lens friction coefficients may (and do) change from test to test, the rank order would stay the same. Unfortunately, this is often not the case, which can often lead to interesting academic discussions and/or conflicting industry marketing materials. As such, it is paramount going forward that in vitro friction methods be clearly described in peer-reviewed literature so that the resulting data is provided in context and, hopefully, future in vitro friction tests become more and more physiologically relevant.

It is also important to remind ourselves that while low friction certainly is important, relevant, and definitely necessary for in vitro comfort, it is likely not the only important variable. Long-term lens interactions with the ocular surface and adnexa, as well as with the tear film, even if supremely lubricous, will continue to be important to study (perhaps within the context of lens friction) in the quest for prolonged comfortable contact lens wear.

From this bioengineer’s perspective, given the importance of in vitro friction on lenses as well as interactions with the ocular tissues and the tear film, the biotribology (study of lubrication, friction, and wear of tissues) of a lens is both an area of interest and a significant opportunity to improve comfort. Having a lens on which the tear film is able to provide sufficient fluid film lubrication (e.g., fluid existing between the lens and tissues, providing lubrication like oil in an engine), in addition to having a low-friction lens surface to provide boundary lubrication (surface-to-surface contact, like a Teflon coating on a pan) and prevent wear/erosion of the eyelid, would be the best of both worlds. Such an ideal lens could conceivably both maintain homeostasis in the ocular environment for longer durations and potentially even restore homeostasis in situations in which the ocular tissues and/or tear film have been disrupted by lens wear (even once removed).

In closing, given the emergence of lenses that enable water to exist at the surface of lenses, as well as the potential use of natural lubricating macromolecules (e.g., hyaluronan, lubricin, lipids, and mucins) present on articulating ocular surfaces, I think a quote by Dr. Eugene Bell pertaining to tissue engineering efforts 14 years ago (Bell, 2000) provides a guiding principle: “We may believe that nature can be imitated biologically, but is it difficult to conceive, however imperfect nature is, that it can be improved.” CLS

For references, please visit www.clspectrum.com/references and click on document #229.

Acknowledgements: Canada Research Chairs Program, Natural Sciences & Engineering Research Council of Canada, and Canadian Institutes of Health Research.

Dr. Schmidt is an associate professor in Engineering and Kinesiology at the University of Calgary and is a Canada Research Chair in Biomedical Engineering – Biomaterials. He has financial interests in Lubris, LLC and is a consultant or advisor to Allergan and Johnson & Johnson.