How many times have you heard from patients that they think they are allergic to their new “super oxygen-permeable” silicone hydrogel (SiHy) lenses? A quick search of the internet will show a number of patient blogs in which such opinions are commonly expressed. So, how likely is it that patients could be allergic to their SiHy lenses?
Allergy in General
Let’s begin by defining what “allergy” means. It was first described in the early 1900s by Clemens von Pirquet after he noted that some of his patients were hypersensitive to innocuous substances such as dust, pollen, or certain foods. Simply, an allergy is an abnormal over-reaction by a person’s immune system against a normally harmless substance; the body reacts by releasing chemicals that cause classical allergy symptoms and signs. Allergic diseases include hay fever, atopic dermatitis, food allergies, and allergic asthma. Common allergens include pollen, animal dander, food (e.g., peanuts and shellfish), metals, and insect stings.
Studies suggest that approximately 50% of children and adults tested for allergies in the United States show a positive response (Arbes et al, 2005; Zug et al, 2008). In addition, allergies are generally on the rise globally, particularly in the Western world (Platts-Mills et al, 2005; Anandan et al, 2010).
The Allergy Reaction
To determine whether an allergy to the silicone within SiHy contact lenses is possible, we must understand how allergic reactions occur. The underlying mechanism ultimately involves immunoglobulin E antibodies (IgE), part of the body’s immune system, binding to the allergen to which the person has been exposed and then to a receptor on mast cells or basophils. That triggers the release of inflammatory chemicals such as histamine, resulting in the classical symptoms and signs seen in allergic responses (Hall et al, 2014; Murphy and Weaver, 2017).
We know that this immune response is triggered as a defense mechanism, but how does the immune system know to respond to an impending attack by a substance that may cause it harm? Because life on Earth is carbon-based, the immune system is “wired” to only recognize molecules that have a carbon-based chemistry (such as proteins, sugars, and nucleic acids), as that may signal attack by microorganisms. Sugars and nucleic acids serve as signals to warn that a pathogen is present, which then triggers an innate immune response that recognizes general features of microorganisms (Iwasaki and Medzhitov, 2010). In comparison, proteins from pathogens are recognized by the adaptive immune system, which utilizes antigen receptors that are highly specific (Iwasaki and Medzhitov, 2010), targeting those pathogens for destruction. Silicones, also known as polysiloxanes, are synthetic polymers made up of repeating units of siloxane, which is a chain of alternating silicon and oxygen atoms. Thus, silicone has none of the properties that would elicit a true allergic response and thus cannot produce an allergic event in isolation.
Is It an Allergy?
The concept of “silicone allergy” stems from interactions of silicone-based biomaterial applications in body sites other than the eye, notably silicone breast implants. Some studies have suggested that anti-silicone antibodies (mainly IgG) are present in patients who have (or have had) silicone breast implants (Wolf et al, 1993; Bekerecioglu et al, 2008). However, these findings remain controversial, as other studies have reported the low likelihood of anti-silicone antibodies (White and Klykken, 1998; Klykken et al, 2008) and no discernible difference in IgG binding to silicone in patients who have silicone breast implants compared to those who don’t (Oliver et al, 2000).
Levy and colleagues (2009) performed a critical review of the literature regarding anti-silicone antibodies and concluded that most studies suggest that silicone implants cause nonspecific foreign body reactions. There have been a small number of case reports in the literature pertaining to silicone “allergic” responses. However, these case reports invariably turn out to be either not true allergic reactions (as there are no IgE antibodies involved) (Hunsaker and Martin, 1995; Rubio et al, 2009) or are due to other types of hypersensitivity reactions, often attributable to impurities in the silicone, such as metals (Cantisani et al, 2007) or silicone-protein complexes (Kossovsky et al, 1987).
Thus, a careful literature review would suggest that “allergy to SiHy lenses” is a myth. The silicone moieties within SiHy lenses remain tightly bound within the polymeric structure of the lenses and do not leach or leak from the lenses. And, even if they did, they do not possess the necessary characteristics to elicit an allergic response.
Of those patients who have allergies, about 20% demonstrate ocular allergy (Abelson et al, 2002). This includes acute conditions, such as seasonal and perennial allergic conjunctivitis, and chronic conditions, such as vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis (GPC) (Abelson and Schaefer, 1993; Friedlaender, 1993; Donshik et al, 2008; Koh, 2017).
The major symptoms and signs that accompany these conditions include ocular itching, lacrimation, mucous discharge, hyperemia, chemosis, and, in severe cases, swelling of the conjunctiva and corneal infiltrates. Wearing of SiHy lenses has been linked to a number of inflammatory complications that may mimic these presentations, including discomfort.
While comfort remains largely similar between SiHy and hydrogel lenses in reviews (Guillon, 2013; Jones et al, 2013; Stapleton and Tan, 2017), several reports actually show it to be higher with SiHy lenses used on a daily wear basis (Dumbleton et al, 2006; Riley et al, 2006; Dillehay and Miller, 2007; Young et al, 2007; and others. Full list available at www.clspectrum.com/references .). Other inflammatory complications include itching (Skotnitsky et al, 2006), infiltrative keratitis (Szczotka-Flynn and Diaz, 2007; Radford et al, 2009; Chalmers et al, 2010; Chalmers et al, 2011; and others), contact lens-associated papillary conjunctivitis (CLAPC) (Dumbleton, 2002; Skotnitsky et al, 2002; Skotnitsky et al, 2006; Donshik et al, 2007; and others) (Figure 1), and acute red eye (Dumbleton, 2002; Willcox et al, 2004; Stapleton et al, 2006) (Figure 2).
However, as outlined earlier, this type of allergy is not biologically possible (Hall et al, 2014). Yet, some eyecare professionals still point to “silicone allergy” as a reason. If allergy isn’t the reason, then why do such complications occur?
SiHy lenses were commercialized in the late 1990s in an effort to permit safe overnight wear. These materials provide greatly improved oxygenation to the cornea and have largely eliminated any form of hypoxic signs, whether worn on a daily wear or overnight basis (Covey et al, 2001; Sweeney et al, 2004; Stapleton et al, 2006; Sweeney, 2006). SiHy materials have shown steady market growth and now account for > 70% of all new fits in many global markets (Morgan et al, 2017).
Despite these oxygen benefits, early-generation SiHy materials did result in some challenges due to the inherent bulk and surface changes that occurred through the incorporation of siloxane groups.
In addition to increased oxygen transport, the major bulk property that differed from hydrogel materials was lens modulus. The incorporation of siloxane groups increases the modulus and stiffness of SiHy lenses (Jones et al, 2006; Horst et al, 2012; Tighe, 2013), resulting in a number of mechanical complications (Dumbleton, 2002 and 2003; Lin and Yeh, 2013), particularly with lower-water-content SiHy lenses that have the highest modulus (Tighe, 2013). These mechanical complications include the aforementioned CLAPC (Figure 1), which may mimic an allergic response but is largely mechanical in nature (Skotnitsky et al, 2002; Skotnitsky et al, 2006; Sorbara et al, 2009).
First-generation SiHy materials were developed for the extended wear market, whereas more recent SiHy materials are intended for daily wear, particularly daily disposable SiHy lenses, which are not approved for overnight use. Figure 3 shows that many recent SiHy lenses have modulus values that are much closer to those found in hydrogels, and these appear to have overcome many of the mechanical problems seen with earlier SiHy lenses.
SiHy materials also differ in their surface properties, impacting both wettability and deposition. In vitro (laboratory-based) studies suggest that SiHy materials are more hydrophobic compared to hydrogels, with higher contact angles being reported (Jones et al, 2006; Lorentz et al, 2007; Read et al, 2011; Menzies and Jones, 2012; and others).
However, in-eye data would suggest that the wettability of hydrogel and SiHy lenses is largely similar (Keir and Jones, 2013), and attempts to correlate in vitro contact angles with comfort or in-eye wetting have been largely unsuccessful. Reports do exist linking in-eye wettability with comfort (Truong et al, 2014).
Deposition profiles also differ between SiHy and hydrogel materials, with SiHy lenses exhibiting increased amounts of lipids (Lorentz et al, 2007; Carney et al, 2008; Pucker et al, 2010; Walther et al, 2011; and others) and lower amounts of proteins (which are often denatured) compared with hydrogel lenses (Senchyna et al, 2004; Subbaraman et al, 2006; Suwala et al, 2007; Luensmann and Jones, 2012; and others). While trying to link lens deposition with comfort and performance would seem natural, recent reviews have struggled to provide any solid evidence that increased deposition results in reduced comfort (Jones et al, 2013). However, many practitioners have certainly experienced situations in which they have transitioned a patient from successfully wearing a hydrogel material into a SiHy and been unable to obtain similar levels of comfort, wettability, or wear time, resulting in them returning to a hydrogel material (Chou, 2005).
Data also exist concerning the relative rates of inflammatory complications between these two categories of materials. Several reports have demonstrated that wearing SiHy materials on a reusable basis results in an almost two-fold increase in the relative risk for infiltrative keratitis (IK) (Szczotka-Flynn et al, 2007; Radford et al, 2009; Chalmers et al, 2010; Chalmers et al, 2011; and others). The reasons behind this increase in infiltrates for reusable SiHy lenses remain a subject of intense debate, but factors may include the increased modulus, reduced wettability, altered deposition patterns, and interactions with lens care solutions (Jones et al, 2002; Andrasko and Ryen, 2007; Carnt et al, 2007; Papas et al, 2007; and others) and cases (Willcox et al, 2010; Wu et al, 2011; Willcox, 2013; Dantam et al, 2016).
The question remains as to what causes the clinical problems that are often related to “allergy” when practitioners either fit or refit patients into SiHy materials (Table 1). One unequivocal truth is the fact that the eye is not allergic to the silicone in the lens. However, the silicone components may cause binding of a wide variety of substances to which the eye can react.
|CLINICAL COMPLICATION||POTENTIAL CAUSE|
|Reduced comfort||Reduced in-eye wettability
Increased deposition with lipid or denatured protein
|CLAPC||Mechanical cause due to increased modulus of SiHy lens or to poor fit
Inflammatory reaction to denatured protein on the lens
|IK||Inflammatory reaction to lens contamination with tear film components, solution components, or bacteria from the ocular adnexa or contact lens case|
|Acute red eye||Inflammatory reaction to lens-bound bacteria|
Considering the problems in Table 1, one solution could be to prescribe contemporary SiHy materials on a daily disposable basis. However, examination of prescribing data shows that SiHy materials are prescribed much more for reusable lenses than for daily disposables (Morgan et al, 2017). This is likely due to a combination of cost, reduced parameter availability, and a misguided perception that oxygen needs are more relevant when lenses are reused than when discarded every day. However, if lenses are worn for a similar period of time (all day), then why should oxygen needs differ between a reusable and a daily disposable modality? While this decision can be defended for part-time wearers, full-time wear should be given the same oxygen considerations regardless of the frequency of replacement.
Thus far, the published data on the performance of daily disposable SiHy lenses state that they provide excellent levels of comfort and physiological response (Varikooty et al, 2013; Szczesna-Iskander, 2014; Chalmers et al, 2015; Varikooty et al, 2015; and others), that the levels of IK are no different between SiHys and hydrogels (Chalmers et al, 2015; Diec et al, 2017), that deposition is markedly reduced compared to reuse of the same material (Subbaraman et al, 2006; Suwala et al, 2007; Hall et al, 2013; Walther et al, 2013; and others), and that daily disposable SiHys compare favorably to the performance of daily disposable hydrogels (Diec et al, 2017; Ruiz-Alcocer et al, 2017), with increased limbal hyperemia being present in some wearers of the hydrogel materials (Diec et al, 2017).
An often stated reason for not prescribing SiHy lenses relates to clinical issues that are attributed to an inability to wear a siloxane-based lens material. However, as previously stated, clinicians do a disservice to their profession, their scientific training, their patients, and to the contact lens industry by invoking the phrase “silicone allergy” as an explanation for problems that patients might encounter with SiHys.
Many issues that patients experience while wearing SiHy lenses occur because of tear film issues that can often be overcome by switching to a daily disposable SiHy lens. There will always be some patients who experience comfort problems with certain contact lens solutions, rewetting drops, and lens materials, whether they be hydrogel or SiHy lenses. However, this applies to many products and is not—in the case of SiHy materials—due to allergy to the material. CLS
For references, please visit www.clspectrum.com/references and click on document #270.
Acknowledgement: This manuscript was funded by CooperVision through an educational grant.