WHILE THERE HAS BEEN A steady increase in the uptake of daily disposable lenses over time, almost 50% of contact lens wearers continue to wear reusable lenses and require the use of contact lens care solutions (CLCSs).1,2 The modern CLCS is entrusted to perform multiple tasks, a feat all the more impressive when considering their usability and effectiveness in performing those tasks when used by the general public.
CLCSs have to disinfect the lens and reduce the amount of microbial contamination to an acceptable level for safety; clean the lens by removing deposits, such as proteins and lipids, for health; and recondition lenses so that they are comfortable to wear following disinfection, all while doing so in a manner that is accessible to a wide audience. When considering all of these functions, the fact that multiple solutions are commercially available is remarkable. This article will provide some insights into the composition and performance of different components in a CLCS.
BIOCIDES, PRESERVATIVES, AND DISINFECTION
It is important to distinguish terminology when discussing the antimicrobial performance of CLCSs. The active ingredient(s) incorporated to reduce microbial contamination is most appropriately termed the biocide.3 In contrast, a preservative’s role is to maintain low levels of microbial growth during storage for a period of time. Often the biocide and preservative are one and the same compound, but that does not have to be the case.
The process of contact lens disinfection is intended to rapidly reduce the levels of microbes to an acceptable level. Notably, this does not require complete eradication of microorganisms.3 To demonstrate disinfection efficacy, solutions are typically tested following regimens specified by the International Organization for Standardization (ISO) (ISO 14729), which is submitted to regulatory authorities such as the U.S. Food and Drug Administration (FDA). Guidance from the ISO standard specifies the conditions, the panel of microorganisms to test against, and how results should be interpreted, before a CLCS can be approved for use.3
Initial testing uses the “stand-alone” method, which examines whether the solution can achieve an acceptable reduction in microbial activity when microorganisms are introduced. If it is unable to achieve this, then the “regimen” test is typically employed, in which contact lenses are contaminated with microorganisms and then processed with the disinfection steps recommended by the manufacturer, which may include actions such as rubbing and rinsing.4
Reducing the microbial contamination to an acceptable level through either the stand-alone or regimen test is sufficient to demonstrate antimicrobial efficacy.4 However, it is noted that the current panel of organisms for these tests consists of bacteria and fungi and does not include viral or protozoan examples such as Acanthamoeba.4-7
A typical conceptual split when considering CLCSs is between multipurpose solutions (MPSs) that can be placed directly on the ocular surface and others that require some type of neutralization prior to contact with the eye.3
MPS has a usability advantage for patients, as it requires the use of only one solution to clean, condition, and disinfect worn lenses. This usability advantage is reflected in the dominant proportion MPSs have in the CLCS market in different countries, with MPS usage ranging from 80% to 100% of systems prescribed by clinicians.1,8
This simplicity, however, can provide a design challenge, as manufacturers have to carefully balance antimicrobial activity through selection and concentration of biocides with ocular surface compatibility.3 Examples of biocides in MPS include polyhexamethylene biguanide (PHMB) (molecular weight [MW] 1,500-2,000), polyquaternium-1 (PQ) (MW 7,000), Aldox (MW 300), and alexidine dihydrochloride (MW 500).3
In many contemporary examples on the market, a combination of these biocides is selected to provide the best balance of biocompatibility to the ocular surface and efficient and effective disinfection. Common biocide combinations include PQ with Aldox and PHMB with PQ; some MPSs combine three different biocides (PQ, alexidine, and PHMB)3 (Table 1).
The MW of the biocides in MPSs deserves some scrutiny, as it has been demonstrated that low MW biocides such as alexidine, and even PHMB, can be taken up to a significant degree by lenses during the soaking step.9-11 This appears to decrease the antimicrobial activity of the remaining solution by reducing the biocide concentration, and is of greater concern when lenses are stored for longer periods of time.9,12,13
In comparison, solutions based on PQ, with a larger MW, do not appear appreciably to change biocide concentration when contact lenses are placed within them and, thus, are better able to maintain their antimicrobial activity over time.9This may be one reason why many currently available MPSs include PQ and/or include a combination of biocides rather than relying solely on one, which may become depleted for some reason.
Hydrogen peroxide-based solutions are an example of non-MPSs used with contact lenses. These products utilize 3% hydrogen peroxide as an oxidative disinfecting agent.14 This concentration cannot be placed directly on the ocular surface and requires some method of neutralization prior to contact lens reapplication.
Neutralization of hydrogen peroxide has been facilitated with methods such as platinum disc incorporation into the lens case or the addition of enzymatic tablets such as catalase.14 The rate of conversion of active hydrogen peroxide into water and oxygen varies across the different methods, but in most systems it is complete within one hour. However, to ensure complete conversion and minimize the potential for ocular toxicity, most manufacturers recommend that lenses only be reapplied after at least six hours of exposure, at which time the solution consists primarily of saline.14
Storage of the lenses after disinfection in a neutralized solution that is essentially saline presents a significant advantage as well as a potential concern. It allows for the least amount of exposure of the eye to chemicals from the CLCS, a benefit for practitioners or patients concerned with managing potential toxicity or health issues of the ocular surface. This line of thinking often leads to a switch from MPSs to hydrogen peroxide-based solutions by practitioners when troubleshooting issues surrounding contact lens discomfort.14 The downside to this storage in neutralized peroxide is that the concentration of hydrogen peroxide is so low that it no longer acts as an effective preservative, allowing for the potential of microbial growth when lenses are stored for long periods.14
Instructions for use of these hydrogen peroxide-based solutions typically recommend that they can be safely stored in the neutralized solution, without being reopened, for up to seven days, after which they should be disinfected again.14 Retrospective analysis comparing patients using an MPS versus hydrogen peroxide solutions have suggested that while the rate of complications and serious infections of the cornea, such as microbial keratitis, are similar, hydrogen peroxide users are less likely to report discomfort.15
Even with these benefits, the market share of hydrogen peroxide systems is low, at under 20% in most countries.1,8 It is speculated that this may be due to the greater complexity of using the system and the fact that the solution cannot safely be placed directly on the eye.1
The most recent development in biocides in CLCSs has been the use of povidone iodine (PI). PI is commonly used in medicine and ocular management, such as in disinfection of the eye and surrounding adnexa in preparation for ocular surgery, and off-label for the management of adenovirus ocular infections.16
PI is prized as a disinfectant, as it has a broad range of activity against bacteria, fungi, and viruses, as well as protozoans such as Acanthamoeba.17 It exerts this antimicrobial action via intracellular oxidation of proteins, nucleotides, and other molecules, causing cell death.18 However, similar to hydrogen peroxide, it cannot be placed directly on the eye without causing toxicity and must be first neutralized in some way.
In the commercially available PI CLCSs, neutralization is facilitated by a tablet, case, and diluting solution.17Interestingly, the tablet is of key importance for both the PI’s disinfection properties and its neutralization. The tablet contains two layers. The outer layer contains PI, while the inner part contains ascorbic acid (vitamin C) and protease.17Adding the tablet to the diluting solution (approximately 8mL) causes rapid dissolution of PI into the solution, rapidly raising levels to antimicrobial levels. This is also accompanied by a color change to dark brown, providing a visual indication of the presence of PI and warning that the solution or lenses should not be placed on the eye. Ascorbic acid in the inner core is released after five minutes of soaking and rapidly neutralizes the PI, rendering the solution colorless after 20 minutes. The protease released at this time then serves to help remove proteins from the lenses. To ensure that disinfection, neutralization of PI, and adequate protein removal occur, the minimum recommended soaking time of lenses in this CLCS is four hours, regardless of the change in color observed.17
Performance of this new PI CLCS has been evaluated in several different contexts, both in the laboratory and clinically. The PI solution is demonstrated to be effective in the stand-alone test, adequately reducing microbial bioburden without any other actions.17 Adding rubbing and rinsing steps to the cleaning regimen with this solution leads to even fewer viable microorganisms being recovered, demonstrating the effectiveness of the regimen in addition to the care solution.17
The efficacy of the PI-based solution has also been explored in vitro when including other complicating factors, such as organic soil or denatured protein contamination of lenses.19,20 The PI system in most instances continues to show remarkable disinfection performance, even in the presence of these contaminants in solution or when deposited onto rigid contact lens materials.19,20
In contrast, disinfection performance of the MPS examined in these studies is greatly decreased by the presence of these additional contaminants.19,20 Clinically, the PI system has reportedly been well tolerated when used in a daily wear context, reducing corneal staining compared to habitual MPSs used by participants in the study and with low rates of adverse events.21 Case contamination by microorganisms from participants using the PI system is also low, with 30% of the cases recovered from participants having no detectable microbes and the rest only having very low levels.21
Early in the COVID-19 pandemic, the potential for the eye and contact lenses being a vector for disease transmission was raised, albeit while lacking any evidence.22 This, however, did highlight that the antiviral activity of contemporary CLCSs are not routinely tested for in regulatory approval pathways. There have now been several reports investigating the ability of CLCSs to disinfect against model coronaviruses such as the coronavirus mouse hepatitis virus or seasonal human coronaviruses.5-7
Interestingly, the conclusion reached by several studies appears to be that while oxidative care solutions such as those based on hydrogen peroxide and PI are able to inherently neutralize viral particles, MPSs are typically unable to do so.5,7 However, the viral particles in these laboratory studies appear to be poorly adherent to contact lens materials, and inclusion of a simple rinse step, as would be recommended as part of the rub and rinse regimen for MPSs, has been shown to be sufficient to reduce the recovered viral particles from contact lenses below the limits of quantification.6,7The message to practitioners is that they should emphasize to patients the importance of following the manufacturer’s instructions when using their care systems, whether they be MPSs with a rub and rinse or an oxidative system requiring neutralization before lens use.
CLEANING AND RECONDITIONING
Other than decreasing microbial bioburden on worn lenses, CLCSs also have a role in reconditioning lenses so that they remain comfortable to use until replacement. This cleaning and reconditioning can have different aspects, including the removal of deposits such as proteins or lipids and conditioning the lens surface to reduce its friction or improve its comfort when re-worn.3 The broad compatibility of the available CLCSs with a wide variety of contact lenses highlights the work that has been done to optimize their effectiveness with lenses of different materials.
For example, traditional soft hydrogel contact lenses are known to deposit more proteins compared to lipids.23 In contrast, certain silicone hydrogel (SiHy) lenses—due to the greater levels of hydrophobicity on their surfaces—tend to deposit greater amounts of lipids compared to conventional hydrogels, and the small amount of proteins deposited tend to be denatured.23-26 Rigid lenses and orthokeratology lenses that are used for longer periods of time before replacement seem to build up more stubborn deposits, which may be more difficult to remove.20
CLCSs typically employ some combination of salts, buffers, surfactants, chelating agents, and wetting agents, as well as occasionally some dedicated deposit removers such as enzymes, to aid with the reconditioning process.3,27Surfactants include additives such as those in the Tetronic and Pluronic families that have both hydrophilic and hydrophobic components, allowing for them to solubilize hydrophobic lipids on the lens surface into solution to be removed.27,28
Chelating agents are used to sequester different metal ions, often to support the activity of other components such as the biocides or the surfactants. The solution will also need the necessary salts and buffers to ensure that the pH and osmolarity remain in the correct range, with borate and phosphate buffers being common.3
A lubricating agent will attract moisture to the lens surface, and CLCSs include common additives such as hyaluronic acid, hydroxypropyl methylcellulose, and polyvinyl alcohol.29 Wetting agents reduce the amount of energy needed for a hydrophilic agent to be in contact with the surface, theoretically increasing comfort when worn.
In many CLCSs, the surfactants within the solution serve dual roles, both removing some deposits and acting as a wetting agent.3 Recent developments in surfactants have attempted to aid in maintaining hydrophilic surfaces on inherently hydrophobic surfaces, such as on SiHy lenses. Here, the introduction of solutions containing polyoxyethylene-polyoxybutylene (EOBO) have been shown to condition SiHy lenses to maintain resistance against hydrophobic lipid deposition.30
CLCSs should also be carefully considered for more specialty lenses. Large-diameter scleral lenses are a good example of this: while they can typically be managed with MPS- or peroxide-based CLCSs, some additional features may influence these choices.31 In many instances, a coating of polyethylene glycol may be added to the surface to increase hydrophilicity, but this coating may be damaged if alcohol-based or abrasive cleaners are used, which would lead to inconsistent wettability of the lens surface.32
Scleral lenses also require a solution within the lens as an interface when worn. Importantly, while MPSs are compatible with the ocular surface, considering that the solution within a scleral lens remains in contact with the ocular surface while it is being worn, unpreserved saline, which is avaialble in commercial formulations marketed for scleral lens use, is recommended for this purpose.31
SUMMARY
Clearly, the formulation of modern CLCSs is complex, from selection of biocides for disinfection to agents to help clean and recondition lenses for reuse. CLCSs come in different forms, such as MPSs or oxidative systems, each with its own advantages and disadvantages, which should be considered when they are prescribed or recommended so that patients are best served while wearing reusable lenses.
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