THERE HAS BEEN A considerable evolution of the definition of the term “biocompatible” over the past few decades, as research into biomaterials and their interactions with living systems has accelerated.1 In the broadest definition, biocompatibility can be defined as “…the ability of a material to perform with an appropriate host response in a specific situation.”2
When considering biocompatibility within this very general definition, a few key concepts become evident. The first is that the material being used or tested must “perform.” That is, the material must have some type of intended function when used within a living system, not simply tested to see whether it provokes a response from the host.
This general definition hints at not only an intended purpose, but also specific situations in which the material is to be implemented, suggesting that evaluation of biocompatibility may be impacted by how the device is intended to be used in a biological system, and indeed, the biological system’s response to it.3
The definition also mentions a host response, and more specifically, an “appropriate” host response, to the use of the biomaterial.2 This suggests the complex nature of the use of any foreign substance in the body that may provoke an immune or inflammatory response, lessening its utility. On the other hand, some materials have been specifically engineered to stimulate a desired host response, such as those designed to support tissue regeneration and repair.3
In terms of biocompatibility, the performance of contact lenses can be evaluated from both historical and modern perspectives. Contact lenses obviously have intended purposes and indications, such as the correction of ametropia, including myopia, hyperopia, and astigmatism, as well as less common indications for medical application.1 There is little argument that contact lenses are successful in performing these intended purposes, considering the number of wearers worldwide, which exceeds 140 million.1
Significant recent research and development centers on the ability of the contact lens to elicit an appropriate host response. In the evolution of contact lenses—from the initial glass molds to today’s custom cut or readily available off-the-shelf lenses—each advancement has been a direct response toward trying to alleviate an issue of contact lens wear and biocompatibility.
In many historical examples in the development of contact lenses, various materials have been able to achieve enough initial biocompatibility to allow their use on a short-term or medium-term basis.4 Many new contact lens developments have occurred in response to biocompatibility issues that have been identified after longer periods of lens wear but may not have been initially apparent with new materials used for making lenses.
For example, the introduction of polymethylmethacrylate (PMMA) lenses to replace glass lenses allowed for significant improvement in wearability, eliminating the need for topical anaesthetics when wearing glass lenses for even short periods.5 However, with longer wear times with PMMA being possible, new issues of biocompatibility were identified, specifically lack of oxygen transmission to the cornea.5
Thus, it could be argued that the biocompatibility of PMMA depends on how long it is used, as it is only after a period that the unsuitability of this material for contact lenses becomes apparent. This reflects the aspect of biocompatibility that denotes the use of the device in a “specific situation.” Although PMMA lenses may be considered not biocompatible for long-term contact lens wear, they may still be useful and biocompatible for other applications, such as trial lens fitting, where their short-term use may be more acceptable.
Developments in contact lens materials since the introduction of PMMA have arguably followed similar patterns; issues identified with the wide release of new lens materials and wear paradigms have led to identifying new problems with biocompatibility. GP lenses incorporated silicone and fluorine elements into rigid lens designs, allowing for significantly more oxygen transmission compared to PMMA when worn.5 Unfortunately, neophyte contact lens wearers still found them uncomfortable to wear, at least initially, necessitating adaptation periods and requiring more motivation from patients.5
Soft contact lens materials made from hydrogels offer significantly more initial comfort than rigid lenses, leading to their widespread popularity and challenging chemical engineers to balance their comfort, handling characteristics, oxygen transmission, dimensional stability, and fabrication reproducibility.4
The oxygen transmission of traditional soft contact lenses is limited by the lenses’ water content, which cannot be raised too high without compromising the handling and integrity characteristics of the lenses.1 During regular daily wear of hydrogel lenses, the upper limit of oxygen transmission due to the lenses’ water content is generally sufficient; however, this is not the case in a closed-eye environment, in which insufficient oxygen leads to corneal swelling.1
At this time, the challenge to the industry was to develop a soft lens to be worn in a closed-eye environment without causing corneal swelling, and this led to the development of silicone hydrogels lenses. The hope was that these new lens materials would significantly improve oxygen transmission, allowing for extended wear and alleviating the need for cleaning, disinfection, and reconditioning.5
Silicone hydrogel lenses have been successful in reducing the rates of hypoxia-related complications like corneal swelling and vascularization. Indeed, many contemporary practitioners have only ever practiced with silicone hydrogels, so their exposure to hypoxia-related complications is likely to be limited. Unfortunately, silicone hydrogels did not usher in an era of extended wear as the “default” mode of contact lens wear. Other complications, including inflammatory and infectious conditions, have been observed with overnight wear despite the improved oxygen transmission of the silicone hydrogels, limiting this wear modality.6
However, silicone hydrogels have found significant success as part of daily wear schedules, whether in a reusable context, in which the lens is cleaned and reconditioned before re-wear, or in daily disposable wear, in which it is worn once before being discarded. Despite these continued improvements in biocompatibility, dropout or discontinuation from contact lens wear continues to be an issue for some people.
Rates and Reasons for Contact Lens Dropout
Systematic reviews of contact lens dropout have reported a mixed set of evidence and conclusions within the literature, complicating the pathways for both clinicians and the industry to combat the problem. Contact lens dropout is estimated to be 21.7%.7 Ocular symptoms and ocular discomfort are the most commonly cited reasons for contact lens discontinuation across several studies.7
It was hoped that, with the introduction of silicone hydrogel materials and their increased oxygen transmission, there would be improvements in ocular health and thus comfort. However, surveys of contact lens dropout since silicone hydrogel lens introduction have not shown significant changes in either the rates or reasons for discontinuation, which continue to be discomfort and ocular symptom-related.8,9
In comparing patients who discontinued contact lens wear in the past year due to discomfort with age-matched and sex-matched successful contact lens wearers, dry eye was found to be a significant factor in predicting dropout.10Specifically, worsening grades of meibomian gland plugging, upper eyelid meibum quality, and tortuosity were identified as factors that increased the rate of contact lens dropout.
Interestingly, the length of contact lens wear and the type of contact lenses worn may affect whether discomfort is identified as the primary cause of lens discontinuation. Neophyte lens wearers who discontinue lens wear tend to do so within the first 2 months of starting contact lenses, and the most frequently cited reason are issues with distance vision (26%) or near vision (16%), discomfort (14%), and handling (15%).11
When further stratifying patients within this study, it was found that there is a clear separation in terms of reasons for discontinuation between spherical vs toric or multifocal wearers. For spherical contact lens wearers, handling and comfort were the most cited reasons for discontinuation; toric and multifocal wearers cited issues with vision.11
Finally, when examining neophyte scleral lens wearers, perhaps unsurprisingly, handling issues were the top cited reason for dropout, followed by discomfort.12
Factors Affecting Long-Term Contact Lens Success
Although there has been significant discussion in the literature surrounding the factors associated with contact lens dropout or the success of new contact lens fits, comparatively few studies have specifically investigated the factors associated with long-term contact lens success.10 The majority of studies have focused on comparing the differences between successful contact lens wearers, defined by their ability to wear contact lenses for acceptably long periods of time throughout the day, several days per week, to those who have dropped out.13
The age of participants, and more specifically the age at development of presbyopia, is also recognized as a factor in lens wear discontinuation, even if it is not explicitly investigated.13 In many instances, studies of contact lens dropout exclude patients above the age of 45 years to remove vision issues due to presbyopia as a factor influencing contact lens dropout.13
As such, the literature seems to suggest that there are 3 main areas to focus on for identifying the factors associated with success or dropout of contact lenses. First are individuals who drop out early in their contact lens wear journey; new wearers who drop out tend to do so within the first 2 to 6 months. Second are those who discontinue due to vision issues associated with presbyopia, because maintaining acceptable vision remains a challenge for most of this group. Finally, there is a middle group between these two who discontinue contact lenses after a period of lens wear, most likely due to discomfort.
Practitioners should be proactive in investigating and querying patients about dryness or discomfort symptoms when wearing contact lenses, even seemingly successful contact lens wearers, as this may present obstacles to successful lens wear in the future.14
Back to the Bench
There have also been significant developments in the methods and tests used to evaluate contact lenses within the laboratory to try and identify—at the bench level—factors that may influence contact lens comfort and, ultimately, long-term lens success. The surface properties of lenses, such as the wettability, coefficients of friction, and influence on evaporation, may impact the lens wearing experience.
More importantly, these factors may be fundamentally affected by being placed into the ocular environment, as components in the tears, including proteins and lipids, can significantly influence these measurements and thus predict the suitability of surface chemistries from laboratory testing.15 Indeed, some of the new understanding of the surface chemistry of lenses has emerged from the increased sophistication of in vitro models testing materials in the laboratory, which often now incorporate artificial tear solutions containing salts, proteins, and lipids to better mimic the tear film and predict how lenses may perform when placed on the eye.15,16
For example, it appears that the shape and structure of the protein deposited on lenses matters more than the overall quantity of protein in influencing the comfort of the lenses.17 In one study, lens deposition of lysozyme, one of the most prevalent proteins in the tear film, was shown to have a strong correlation with subjective comfort.18 This reflects the numerous factors that are associated with biocompatibility, particularly when considering long-term biocompatibility of materials that will be used for spans of days, months, or years, and how some of these factors can be modeled in the laboratory.
The coefficient of friction of contact lenses is another factor to consider when discussing the biocompatibility of lenses and the ocular surface. The coefficient of friction has also been suspected of impacting the wear experience and comfort of lenses.19 The challenge in the field has been the lack of standardized methods for measuring the coefficient of friction between different studies, making comparisons difficult. A call for standardized methods to be developed and utilized is important so that different studies can be made comparable and improvements in this area can be addressed.
Conclusions
Other than intraocular lenses, contact lenses may be considered one of the most successful examples of biocompatible devices used, considering the number of worldwide wearers. The challenge to the sustained growth of the industry is dropout, so further studies focused on optimizing the biocompatibility of lenses should look not only at the factors related to dropout, but also at the factors associated with long-term contact lens success.
Acknowledgments: The author would like to thank Lily Ho, School of Optometry and Vision Science, UNSW Sydney, for her helpful review and comment on this article.
References
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