Disinfection of Contact Lenses
Manal M. Gabriel
Donald G. Ahearn
Soft contact lenses and rigid gas-permeable lenses have provided a practical and safe alternative for eyeglasses. Successful contact lens wear (enhanced vision without irritation) can be achieved during many physical activities unsuitable for glasses. Advanced technologies in biocompatible lens materials, particularly silicone hydrogels, and lens solutions underlie the significant worldwide increases in all types of lens wear over the past two decades. Convenience and comfort have been stimulating factors for increased contact lens wear, but curative usage (eg, treatment of myopia and controlled provision of ocular medications to the cornea) offers further advances.
Contact lens wear in North America is highest in the United States and estimated at near 41 million users.1,2 In Europe, the United Kingdom, Germany, France, Russia, and Italy are estimated, in decreasing order, to include near 100 million users. Brazil, China, and Japan, in the Asia-Pacific region, are leading markets for increased use of contact lenses.
A contact lens placed on the eye is a foreign body that could adversely affect tear flow, its composition, and evaporation. Furthermore, specific lens types may differentially absorb or/adsorb tear components, such as lysozyme, mucin, and lipids, and be impacted by interactions with host ocular tissues and their microbiota. These may also affect the disinfectant efficacy of some multipurpose contact lens solutions.3,4,5,6 In essence, individual ocular homeostasis may be altered to varying extents following lens insertion and the discrete alterations may not be readily observable in the “asymptomatic eye of the wearer.”7,8 Therefore, for avoidance of possible adverse events, successful contact lens wear requires good hygienic practices by the user as guided by clinicians and the manufacturers of these products.
Anoxia (lack of oxygen) damage to cornea tissue as a risk factor for infections (despite being rare) was a primary concern in early conventional soft hydroxyethyl-methacrylate (HEMA) lens wear. This concern, in part, and the quest for development of more biocompatible extended wear (EW) lens materials has stimulated a shift from HEMA type lenses to soft higher oxygen diffusion silicone modalities.9,10,11 The further shift from HEMA lenses and soft silicone EW modalities to mostly daily silicone disposables would theoretically reduce unhygienic lens manipulation and storage12,13; however, the incidence of rare infection and vision loss associated with contact lens wear, at least with bacteria, have not been detected to change overall with the current shift in wear to select higher oxygen diffusion silicone lens types.11
LENS TYPESRigid gas permeable (RGP or GP) contact lenses (copolymers of polymerizable silicone acrylates or fluorosilicone acrylates, and the latter cross-linked with polymerizable hydrophobic-hydrolyzable silicone monomers) have largely replaced polymethyl methacrylate (PMMA) hard lenses. RGP lenses offer clear vision, excellent oxygen diffusion, and durability with ease for cleaning and disinfection. The lenses may be customized for the individual eye shape and worn with comfort; after reasonable adaptation to use, RGPs have increasing applications in orthokeratology, particularly controlling myopia progression.
Conventional hydrogel (soft) lenses first were composed of homopolymers of cross-linked chains of poly(2-hydroxyethylmethacrylate) (pHEMA) with various concentrations of absorbed water. Addition of N-vinylpyrrolidone (NVP) or methacrylic acid (MA) increased hydrophilic properties and related oxygen diffusion.14,15 The polymer type and organization of ionic groups on the hydrogel surface interact with water content and affect the deposition of proteins, lipids, and microorganisms on the lens surface.14,16,17 The backbone chains of the polymers commonly have hydroxyl (—OH), carboxylic (—COOH), esoteric (—COOCH3), or etheric (—COCH3) functional groups. Hydroxyl or polar groups provide the hydrophilicity required for the increased water-swelling activity.
TABLE 53.1 Original US Food and Drug Administration groups of hydrogen lenses | ||||||||||||||||||||||||||||||||||||
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The US Food and Drug Administration (FDA) grouped traditional hydrogel lenses into four major divisions on the basis of ionic charge and water content (Table 53.1). Lenses with nonionic polymers (groups 1 and, particularly, 2) allow more lipid deposition from the tears than hydrogel lenses with ionic radicals (groups 3 and 4). Jones et al14 indicated that high lipid accumulation may be associated with group 2 lenses because of their content, NVP. Group 4 material (ionic, high water content) is more attractive to protein because of the negative charge that methacrylic acid gives to the material. These first groupings served as a guide for probable physicalchemical compatibilities of traditional lens types with their care solutions.
Early silicone hydrogel lenses (such as lotrafilcon and balafilcon, initially grouped in 1 and 3, respectively) and subsequent innovative silicone formulations have deviated in their physical-chemical interaction from the patterns recognized for the above four traditional hydrogel groups. Goals for extending wear time and comfort while addressing potential adverse hypoxia and modulus stresses have guided the shift of soft lens compositions to include mobile siloxy groups of silicone complexed with varied conventional components.17 Also, current silicone soft lenses have gone through several generations of development and modifications in surface properties and treatments and intrabinding of wetting agents.18 Formulation changes among various silicone lens types may differentially alter interactions with host comfort, microorganisms, and solutions.3,5,19 The overall groupings with silicone lenses as discrete types are expected to facilitate the determination of compatibilities with cleaning and disinfection regimens by lens type. A fifth group has been proposed for inclusion of silicone hydrogels and was under evaluation.20
Hutter et al20 proposed a system for silicone hydrogel lens materials that further subdivides group 5 into five subgroups. Group 5-A: low-water content, nonionic, and surface-treated lenses; group 5-B1: low-water content, nonionic, nonsurface treated, and hydrophilic monomer-containing lenses; group 5-B2: low-water content, nonionic, nonsurface treated and semi-interpenetrating network-containing lenses; group 5-C: high-water content and nonionic lenses; and group 5-D: ionic materials, both low-water and high-water content lenses. However, International Organization for Standardization (ISO) 18369-1: 2017 classified group 5 differently as 5A ionic subgroup, 5B high-water subgroup (≥50%), and 5C low-water subgroup, which contains <50%. Representative contact lenses for the five groups are described in Table 53.2.
CLEANING AND DISINFECTANT SOLUTIONSThe selection of chemicals for the cleaning and disinfection of contact lenses requires a compromise between toxicity of the chemicals to the eye and activity against the more
common ocular pathogens. The cleaning step itself can reduce significantly (several logs) the microbial bioburden on a lens.22 Daily cleaners are typically a combination of nonionic or amphoteric surfactants (nonirritating to the eye compared with cationic and anionic surfactants) combined with preservatives and frequently with chelating agents such as ethylenediaminetetraacetic acid (EDTA). Some alcohol-based cleaning formulations (that include approximately 20% isopropyl alcohol) effectively clean and can have some disinfection activity for hard lenses, but because of their toxicity to the eye, they must be thoroughly rinsed from the lens before insertion. Weekly cleaners typically contain proteolytic enzymes (eg, subtilisin-A, stabilized papain, porcine pancreatin) that are designed to remove tear proteins from the hydrogel surface. In combination with daily cleaning, including disinfection with hydrogen peroxide (H2O2), protein deposits and the risk of microbial biofilm formation on hydrogel lenses are reduced with a weekly cleaning regimen. Unit-dose preservative-free saline (15-mL vials) and multidose preservative-free saline also are commercially available for rinsing and for use with heat disinfection units, respectively. Borate buffer in conjunction with certain contact lens care solutions might be essential for optimal preservation (Table 53.3).
common ocular pathogens. The cleaning step itself can reduce significantly (several logs) the microbial bioburden on a lens.22 Daily cleaners are typically a combination of nonionic or amphoteric surfactants (nonirritating to the eye compared with cationic and anionic surfactants) combined with preservatives and frequently with chelating agents such as ethylenediaminetetraacetic acid (EDTA). Some alcohol-based cleaning formulations (that include approximately 20% isopropyl alcohol) effectively clean and can have some disinfection activity for hard lenses, but because of their toxicity to the eye, they must be thoroughly rinsed from the lens before insertion. Weekly cleaners typically contain proteolytic enzymes (eg, subtilisin-A, stabilized papain, porcine pancreatin) that are designed to remove tear proteins from the hydrogel surface. In combination with daily cleaning, including disinfection with hydrogen peroxide (H2O2), protein deposits and the risk of microbial biofilm formation on hydrogel lenses are reduced with a weekly cleaning regimen. Unit-dose preservative-free saline (15-mL vials) and multidose preservative-free saline also are commercially available for rinsing and for use with heat disinfection units, respectively. Borate buffer in conjunction with certain contact lens care solutions might be essential for optimal preservation (Table 53.3).
TABLE 53.2 ISO 18369-1:2017 classification for group 5 silicone lensesa | |||||||||
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TABLE 53.3 Contact lens care solutions | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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The antimicrobial components in current representative multipurpose solutions (MPS) and oxidizing solutions that have addressed FDA and ISO guidelines are listed in Table 53.3. The primary preservative concentrations individually are below standard minimal inhibitory concentrations for most contaminants. However, the presence of unique and proprietary combinations of poloxamers, chelators, and often borates complex in the formulations to provide the overall enhanced antimicrobial and concordant properties of different preservatives. Not all solutions are suitable for all lenses, usages and hygienic approaches or lack thereof.6,23,24,25 The prominent active agents used in contact lens disinfectant formulations are considered in the following text, the structures are shown in Table 53.4.
TABLE 53.4 Disinfectants and their structures | ||||||||||||||||||||
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Hydrogen Peroxide
The H2O2 was the first “nonthermal” system used for the disinfection of contact lenses. The antimicrobial action of H2O2 is particularly based on its dissociated peroxide ion state that is a transitory phase during its decomposition into water and oxygen (see chapter 18). The highly reactive hydroxyl radical oxidizes has been shown to have effects associated with cell membrane lipids, proteins, and DNA. Disinfection solutions are typically at 3.0% concentrations; levels of 1.0% are usually sufficient to eradicate 106 suspended cells per milliliter of the typical cells of the typical challenge vegetative bacteria within 10 minutes, but with certain fungi and their associated spores, the 3.0 % concentration
may require exposures longer than an hour.26,27 When the protozoa Acanthamoeba is the contaminating organism, up to 4 hours of exposure to 3.0% H2O2 may be necessary for acceptable disinfection, particularly due to the presence of cyst-forms.28 The strong biocidal activity of H2O2 combined with its oxidizing-cleaning power and nontoxic decomposition products accounts for its successful application as a disinfectant for contact lenses.
may require exposures longer than an hour.26,27 When the protozoa Acanthamoeba is the contaminating organism, up to 4 hours of exposure to 3.0% H2O2 may be necessary for acceptable disinfection, particularly due to the presence of cyst-forms.28 The strong biocidal activity of H2O2 combined with its oxidizing-cleaning power and nontoxic decomposition products accounts for its successful application as a disinfectant for contact lenses.
The 3.0% H2O2 solution, however, is directly toxic to the eye, and it must be neutralized before a lens can be inserted. Whether the neutralization is by platinum disk, catalase, or sodium pyruvate, the end result is a nonpreserved rinsing solution that is subject to contamination. Microorganisms that may contaminate this solution may produce a biofilm within the lens case or on a stored lens. Cells and associated biofilm can be present on the plastic contact lens case, including the cap area, and in some of these cases may not be directly exposed to subsequent disinfection. Even with direct exposure during disinfection, the cells in the biofilm may survive further the disinfection regimens. The addition of fresh H2O2 will kill most cells in the planktonic state, but cells present in a progressively expanding biofilm in the case, particularly if the substratum is neutralizing, can increase the potential for survival and infection, particularly if disinfected lenses are stored in the case in neutralized H2O2 for several days and then placed on the eye. This same problem exists with lenses disinfected with heat, ultraviolet, or chemicals if the holding solution is insufficiently preserved during the required storage time. Although H2O2 when properly employed may be an efficacious disinfectant for contact lenses, it may cause transient alteration of lens parameters, fading of certain tinted lenses, and requires extended neutralization times for certain lens materials.
Povidone-Iodine
Aqueous povidone-iodine 5% to 10% (see chapter 16) is employed as a surfactant disinfectant prior to corneal surgery with minor toxicity concerns. Commercially available contact lens solutions have exhibited broad antimicrobial properties including the cysts of amoeba.29,30,31,32
Quaternary Ammonium Compounds
In most ocular medications, including antibiotic preparations, quaternary ammonium compounds (QACs) such as benzalkonium chloride (BAK) are used as preservatives (see chapter 21). The QAC molecule (as a type of surfactant) has a hydrophilic head and a lipophilic tail that may range from C8 to C30 branch length disinfectant or preservative BAK preparations containing at least 20% of the C14•H29 homologue and 40% of the C12•H25 homologue.
The polar portion of the molecule is cationic and readily adsorbed to bacterial/fungal cell walls from which the tail portion is inserted (intercalation) into the phospholipid bilayer of the cell membrane. The degree of intercalation is affected by the numbers of C in the tail chain and the cell wall/membrane composition of the target species. BAK preparations may vary somewhat in antimicrobial activity because of homologue differences, but 100 to 200 µg/mL of most preparations in solution cause cell lysis of gram-positive and gram-negative bacteria and fungi. At these concentrations, BAK is used exclusively in contact lens solutions for PMMA and RGP lenses; at least 10-fold dilution of these concentrations is used in solutions for hydrogel lenses. EDTA, a chelating agent with some synergistic potential, is present at concentrations of 0.1% to 0.25% in lens solutions with BAK. Levels of BAK of 1.0 µg/mL may be toxic to cornea tissues33; low concentrations of BAK may absorb to certain lenses and accumulate to toxic levels (see chapter 21).
Polyquaternium-1 (Polyquad)
Polyquaternium-1 is a straight-chained molecule of repeating 4C groups randomly terminated with triethanolamine.
The compound is nonfoaming and relatively nontoxic. Solutions formulated and preserved with this biocide have been employed successfully when used meticulously in a complete regimen of cleaning, disinfection, and storage34; however, it has been reported that microbicidal activity against certain fungi and strains of Serratia marcescens in laboratory test was relatively low.35,36
Myristamidopropyl Dimethylamine
Polyhexamethylene Biguanides
May39 reviewed the use of polyhexamethylene biguanides (PHMB) as in preservative, sanitizer, and disinfectant formulations in various food, water, and clinical applications, including contact lens disinfection systems.40,41 PHMB is a complex of polymeric biguanides with an average polymer length of 5(n) and molecular weight of 3000.42,43
The specific proportion of short to long polymer lengths enhances antimicrobial activity against bacteria, fungi, and amoebae, as does their formulation in a borate buffer with nonionic surfactants. Concentrations of PHMB in all contact lens solutions (because of toxicity) are typically found to be below minimal biocidal concentrations found for challenge microorganisms in laboratory
procedures. For example, a minimum biocidal concentration of PHMB for 106 to 107 cells of Pseudomonas aeruginosa in water with a 1-hour exposure could range from about 20 to 500 µg/mL. Formulations with PHMB may vary in their polymer mixtures in different manufactured lots. The type of poloxamer or nonionic surfactants used as emulsifiers and the presence of chelating agents such as EDTA may have a significant effect on the antimicrobial efficacy of the final formulation.44
procedures. For example, a minimum biocidal concentration of PHMB for 106 to 107 cells of Pseudomonas aeruginosa in water with a 1-hour exposure could range from about 20 to 500 µg/mL. Formulations with PHMB may vary in their polymer mixtures in different manufactured lots. The type of poloxamer or nonionic surfactants used as emulsifiers and the presence of chelating agents such as EDTA may have a significant effect on the antimicrobial efficacy of the final formulation.44
Chlorhexidine
The chemical properties of chlorhexidine and its mode of antimicrobial activity were reviewed extensively by Denton46 (see chapter 22). This cationic bisbiguanide at concentrations of >0.05% (500 µg/mL) is used extensively as a skin disinfectant. At sublethal concentrations, the compound causes cell membrane damage and ion leakage; at lethal concentrations, proteins in the cytoplasm are coagulated. The native compound is poorly soluble in water; thus, the water-soluble gluconate salt is used in contact lens solutions.
Because of the previously mentioned hypersensitivity reactions and toxicity for ocular tissues, contact lens solutions do not typically contain more than 0.006% of the gluconate salt. At these concentrations, inocula of 106 cells of P aeruginosa and Staphylococcus epidermidis were reduced by more than 1 log within 1 minute, whereas more than 3 minutes were required for a log reduction of S marcescens and from 8 minutes to 24 minutes for Candida albicans and Aspergillus fumigatus.47 Chlorhexidine formulations with borate salts have greater antimicrobial activity than chlorhexidine solutions in phosphate buffers (PBS).48,49,50 Isolates of S marcescens may adapt to growth in the latter type formulations, and these adapted cells show increased resistance to BAK and other preservatives.49 Chlorhexidine has demonstrated therapeutic value in the treatment of Acanthamoeba keratitis (AK)51 and is used in the cleaning and disinfection of rigid lenses.
Alexidine
Like chlorhexidine, alexidine (1,1′-hexamethylene-bis [5-(2-ethylhexyl)biguanide]) is a cationic preservative with broad antimicrobial properties for vegetative bacteria, fungi, and amoeba.52 Both compounds are recognized oral and skin disinfectants (see chapter 22). Alexidine, however, has wider applications as a copreservative in formulations compatible with a broader diversity of current contact lens materials.53,54,55,56,57,58
Chlorhexidine and alexidine are structurally similar hydrophobic-lipophilic molecules that bind to lipopolysaccharides and lipoteichoic acids affecting cell membrane integrities that can culminate in cell lysis. Alexidine differs from chlorhexidine in possessing ethylhexyl end groups. Modes and rates of membrane disruption by alexidine vary with cell type and for amoeba and fungi may involve downregulation of mitochondrial-protein tyrosine phosphatase.54,58,59,60,61,62 Alexidine is used in approved concentration of 0.00045%, 0.0002%, and 0.00016% in various contact lens solutions.
Thimerosal
Thimerosal is an organomercurial compound (ethylmercury thiosalicylate) with a broad antimicrobial spectrum but is most effective when used in combination with other preservatives. Penley et al63 found that 106 cells of S marcescens, but not 103 cells, introduced into saline preserved with 400 µg/mL remained viable for 24 hours.
A combination of chlorhexidine (50 µg/mL) and thimerosal (10 µg/mL) produced efficacious D-values for S marcescens (0.22 min) and species of Aspergillus (90 min), Candida (0.67-15 min), and Fusarium (3.0-4.7 min) relatively similar to those of H2O2 in a comparison with other preservatives.64 All these challenge organisms were considered resistant types compared with isolates of Pseudomonas and Staphylococcus. Gandhi et al49 and Parment el al65 found that S marcescens grew in certain chlorhexidine- and BAK-preserved solutions; there is no report of growth of S marcescens in lens solutions preserved both with thimerosal and chlorhexidine. Unfortunately, thimerosal and chlorhexidine have been associated with rare unacceptable incidents of ocular hypersensitivity reactions.66,67 Nevertheless, thimerosal serves as a preservative in limited types of multidose preparations and worldwide topical-ocular formulations with noted activity against certain fungi.68
Chlorine
Tablets of sodium dichloroisocyanurate when dissolved in water are used to release approximately 3 µg/mL chlorine, as a strong oxidizing agent that rapidly inactivate planktonic bacteria via hypochlorous acid and the hypochlorite ion (see chapter 15). These highly reactive chlorine solutions are neutralized rapidly by residual cleaner and organic material and are typically unsuitable for other than short periods of lens storage.
Alcohols
Benzyl alcohol as a disinfection agent for hard and RGP lenses and isopropyl alcohol (propan-2-ol) in a surfactant-based cleaning formulation are examples of the
use of alcohols in current contact lens systems. May et al69 found that cells of S marcescens in the planktonic state and cells of S marcescens and P aeruginosa adhered to lenses survived in an RGP cleaning-disinfecting and storage solutions containing 0.1% benzyl alcohol. Challenge inocula introduced into the alcohol solution were not recoverable within 1 minute. The mode of action is primarily through protein coagulation and dissolution of the cell membrane. The isopropyl cleaning solution is toxic to the cornea, and unless lenses are rinsed thoroughly, their insertion causes immediate eye irritation.
use of alcohols in current contact lens systems. May et al69 found that cells of S marcescens in the planktonic state and cells of S marcescens and P aeruginosa adhered to lenses survived in an RGP cleaning-disinfecting and storage solutions containing 0.1% benzyl alcohol. Challenge inocula introduced into the alcohol solution were not recoverable within 1 minute. The mode of action is primarily through protein coagulation and dissolution of the cell membrane. The isopropyl cleaning solution is toxic to the cornea, and unless lenses are rinsed thoroughly, their insertion causes immediate eye irritation.
Sorbic Acid and Potassium Sorbate
Sorbic acid and its salt, potassium sorbate, are used as preservatives in cleaning solutions and preserved salines, offering protection mainly as fungistatic agents.
The observed activity against bacteria decreases as the pH increases above pH 6.5 (see chapter 12). The unsaturated carboxylic acid is effective in contact lens solutions only in combination with borate buffers or H2O2.
MICROBIAL KERATITISContact lens-related keratitis can be divided into three categories: (1) infectious keratitis with positive cultures; (2) infectious keratitis with negative cultures; and (3) sterile infiltrates, which may result from corneal, hypoxia, or immune-mediated hypersensitivity reactions.70 Changes in the local environment of the eye (eg, pH, corneal hydration, carbon dioxide, and lactic acid production) associated with interactions of hydrogel contact lenses and microbial populations may induce corneal infiltration. It is difficult in many cases to distinguish a slowly developing infectious infiltration from a sterile infiltration. Stein et al71 observed that most (70%) sterile infiltrates and some (35%) infectious infiltrates are less than 1.0 mm in diameter.
The true “sterility” of the cornea mucosa may be questioned by several 16S rRNA gene sequencing studies that demonstrated significant differences in the diversity and abundance of certain bacteria in comparison to traditional culture techniques.72,73,74 These reports seem in general agreement that any commensal component of the cornea mucosa (eg, Delftia) that may not present by routine culture procedures are in low abundance relative to other mucosal tissues of the individual. The relative abundance of the prominent genera in these studies did shift in some instances with contact lens wear.74,75 Commensals in ocular tissue have been projected to elicit protective immune responses for extant microbiota.76 The observed alterations of the ocular/mucosal-commensal microbiome from contact lens wear have not been associated with rare contact lens-associated microbial keratitis (CLMK).
Recent approaches in discerning what factors are the greater risks related to microbial keratitis in lens wear have centered on contaminated lens storage cases and poor lens hygiene practices (over time found with nearly all contact lens users).68 The contact lens may serve as a fomite or, in some cases, a vector in transporting potentially pathogenic microorganisms from a contaminated contact lens case to the eye resulting in rare CLMK.23,77
Incidence
A CLMK is a rare infection that occurs at an overall incidence of about 1 to 4 per 10 000 contact lens wearers per year.78,79,80,81
Epidemiological studies by Morgan et al82 reported a higher incidence of severe keratitis among those who wear hydrogel lenses while sleeping, but the risk for severe keratitis was 5 times lower for silicone hydrogels versus conventional hydrogels.
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