Review of Recent Recalls of Contact Lens Multipurpose Disinfecting Solutions

Professor Mark Willcox, BSc, PhD Mark Willcox is a microbiologist who has specialised in the areas or ocular and oral microbiology. Mark’s research has examined particularly the interactions of the normal microbiota of the eye with contact lenses. In addition, the interactions of the normal and pathogenic microbiota with host defenses has been of interest. Mark has recently begun developing novel antimicrobials and other therapies that will help treat ocular infections. Mark has published extensively in the international literature with over 110 refereed journal articles, 5 patents, 7 reviews, 6 book chapters, 30 conference papers, and over 300 conference abstracts. Mark is a member of several national and international scientific societies including ARVO, International Society for Contact Lens Research, and the Tear Film and Ocular Surface Society. Mark has refereed many papers for several scientific journals and is on the editorial board of Eye & Contact Lens and Current Eye Research.

The past 10 years has seen a dramatic shift in the types of contact lenses and contact lens disinfecting solutions available. Silicone hydrogel lenses were first released around the world in the late 1990s, early 2000s. Since that time there has been an increase in almost all markets of the use of these lenses and they now make up the vast majority of new lenses fits, with lenses being used on daily or extended/continuous wear basis (Woods and Morgan, 2003). Around the same time, multipurpose disinfecting solutions (MPS) were released that allowed users to forego the need to rub lenses to ensure adequate disinfection prior to wear. The disinfection criteria for this new standard (called the Stand Alone test) were published as ISO standard 14729 which has been reviewed by Rosenthal et al. (2002). This new standard required contact lens disinfecting solutions to reduce the load of specific strains of microbes in the solution by specific amounts (1 log reduction for Fusarium and Candida; 3 log reduction for Pseudomonas aeruginosa, Serratia marcescens and Staphylococcus aureus). If solutions passed this Stand Alone test they did not have to met the “Regimen Criteria” that required the solutions to perform to certain standards (including reductions in microbes numbers after rubbing and rinsing the lenses; Rosenthal et al., 2002; Table 1). The rate of use of MPS has gradually increased over the past 10 years to account for >90% of disinfection types in UK or Australia (Morgan and Efron, 2006; Woods and Morgan, 2003). More recently, certain manufacturers have released newer versions of these MPS that have been designed to specifically work with the silicone hydrogel lenses.

Table 1. Comparison of Stand Alone and Regimen Tests for Contact Lens Disinfecting Solutions

NB: No Acanthamoeba strains are tested in either procedure.

However, there have been recent recalls of some of these newer no-rub solutions due to apparent lack of efficacy and consequent increases in specific types of microbial keratitis. On May 15^th 2006, the FDA released a statement announcing that Bausch and Lomb had globally recalled their solution ReNu MoistureLoc (Bausch and Lomb, Rochester, USA; Barry et al., 2006). This followed epidemiological evidence that this solution was linked to an increase in microbial keratitis caused by Fusarium sp. Indeed, in the outbreaks in the USA, there was a 13 times increased risk of Fusarium keratitis in cases compared to controls using ReNu MoistureLoc but not ReNu Multiplus (Chang et al., 2006). In the outbreak in Singapore, 64% of cases used ReNu MoistureLoc (Khor et al., 2006), and the risk using ReNu MoistureLoc was 5 times greater than using ReNu Multiplus (Saw et al., 2007).

Subsequent to the recall, it has been shown that ReNu MoistureLoc solution, as well as some other MPS, show reduced fungicidal activity when a Group IV Acuvue 2 lens had been added to the solution for 6h prior to inoculating the solution with Fusarium (Rosenthal et al., 2006). ReNu MoistureLoc showed 37% reduction in fungicidal activity (Rosenthal et al., 2006). Also, others have shown that reuse of solutions (i.e. simulating wear of lenses and storage in MoistureLoc disinfecting solution) over 2 days resulted in loss of activity against Fusarium of ReNu MoistureLoc and ReNu Multiplus solutions (Levy et al., 2006). Simulating evaporation of both ReNu solutions, showed that MoistureLoc alone lost its disinfecting power against Fusarium sp. (Levy et al., 2006). Interestingly, a clinical isolate from a case of Fusarium keratitis was better able to survive drying and was able to re-grow compared to the ISO recommended ATCC strain (Levy et al., 2006). Similarly, in a separate study, ReNu MoistureLoc but not other MPS, lost much of its anti-fungal activity if it was dried (Zhang et al., 2006). Of course, using disinfection times significantly less than those recommended by the manufacturer results in failure to kill sufficient fungi (Dyavaiah et al., 2007). In these studies, there has been no suggestion that ReNu MoistureLoc fails to meet the ISO Stand Alone disinfection criteria; indeed MoistureLoc was reported as being very effective against bacterial types (Manuj et al., 2006; Hume et al., 2007), or that the type of Fusarium strains isolated from cases (apart from being more robust than ATCC standard strain) were genetically distinct (Levy et al., 2006; Dyavaiah et al., 2007). It appears that it was a combination of the novel ingredients in MoistureLoc (including Alexidine as the disinfecting agent and perhaps Polyquaternium-10, a cellulose polymer) and a certain amount of non-compliance by users that brought about this increase in Fusarium keratitis and the demise of this MPS.

Another recent recall of a MPS solution was made due to an apparent increased risk of Acanthamoeba keratitis. On May 2007, the CDC released a report that demonstrated an increased rate of Acanthamoeba keratitis that was associated with the use of Complete MoisturePlus (Advance Medical Optics, Santa Ana, USA; Bryant et al., 2007). This report demonstrated a 7 times increase in Acanthamoeba keratitis for subjects using MoisturePlus (Bryant et al., 2007). These studies resulted in Advanced Medical Optics voluntarily globally recalling Complete MoisturePlus from sale. Reports have emerged during 2007 of increased rates of Acanthamoeba keratitis in Chicago (Booton et al., 2007), San Francisco (Sansanayudh et al., 2007) and Boston (Tanhehco and Colby, 2007).

As this recall has occurred more recently, there are as yet no reports investigating why this association has occurred. However, there are reports comparing the disinfecting ability of Complete MoisturePlus to other solutions. Table 1 shows the microbes to which MPS need to be active, and as can be seen Acanthamoeba are not part of this set. Thus, the finding that an MPS proved ineffective against Acanthamoeba was perhaps neither predictable nor unlikely. To make matters worse, in the USA there have been changes to water treatment apparently resulting in increased number of Acanthamoeba in household water (Shoff et al., 2007). However, the Acanthemoeba isolates from the Chicago outbreak, much like the Fusarium isolates (see above) were not different to those from other outbreaks in previous years or at different locations (Booton et al., 2007), suggesting that it was simply increased numbers of amoeba in water that lead to increased infections and not change to a more virulent type.

There is some disparity in the literature regarding the efficacy of Complete with studies showing it to be ineffective or partially effective against Acanthamoeba trophozoites (Borazjani and Kilvington, 2005, Shoff et al., 2007) and either ineffective (Shoff et al., 2007, Niszl and Markus, 1998) or effective against Acanthamoeba cysts (Borazjani and Kilvington, 2005) in solution. This disparity seems to be due to the fact that there is no standard method to grow Acanthamoeba in either of its forms (trophozoites or cysts) and the ISO disinfection standards do not require that MPS even be tested against this microbe. However, the inclusion of a ‘rinse and rub’ step either in vitro or during wear of lenses (Seal et al., 1999) results in no Acanthamoeba being cultured from either the lens or the lens storage case. In comparison, other studies with lens cases have shown a 4 – 8% rate of contamination with Acanthamoeba (Larkin et al., 1990, Devonshire et al., 1993, Gray et al., 1995) in comparable populations. One study, examining the efficacy of Complete MoisturePlus against a range of other microbes, has shown that it is comparably active against the standard bacteria (Pseudomonas aeruginosa, Serratia marcescens and Staphylococcus aureus) used in ISO tests, but had reduced efficacy against fungi (Santodomingo-Rubido et al., 2006). Another study demonstrated that Complete MoisturePlus gave an acceptable level of disinfection against S. marcescens (Hume et al., 2007). It seems that the recall of Complete MoistureLoc may have been precipitated by the introduction of new MPS that were no longer recommended to be used with a rub step; a recommendation by manufacturers that probably resulted from lens wearers' wishes. Interestingly, Complete MoisturePlus also contained a cellulose polymer (in this case hydroxypropylmethylcellulose) as did Renu MoistureLoc (Table 2) which is unlike other MPS such as ReNu Multiplus or Optifree Express (table 2) which have not been associated with increased MK risk.

Table 2. Comparison of ingredients in several MPS

Solution		Ingredients
ReNu MoistureLoc (Bausch and Lomb; No longer commercially available)		Alexidine 0.00045%, Poloxamer, Polyquaternium-10, Poloxamine, Hydroxyalklphosphonate, Edetate disodium, Borate and Boric acid, Sodium chloride
ReNu Multiplus (Bausch and Lomb)		Polyaminopropyl biguanide 0.0001% (PHMB), Poloxamine Hydroxyalklphosphonate, Edetate disodium, Borate and Boric acid, Sodium chloride
Complete MoisturePlus (Advance Medical Optics; No longer commercially available)		Polyhexamethylene biguanide (PHMB) 0.0001%, Poloxamer 237 (0.05%), Hydoxypropyl methylcellulose, Edetate disodium, Sodium chloride, Potassium chloride, Taurine, Phosphate buffer
Optifree Express (Alcon Inc, Fort Worth, USA)		Polyquaternium-1 (Polyquad) 0.001%, Myristamidopropyldimethylamine (Aldox) 0.0005%, Poloxamine, Sodium citrate, Boric acid, Sorbitol, Aminomethylpropanol, Edetate disodium

In conclusion, the apparent failures of two MPS systems over the past year or so are likely to be the result of a combination of effects including the wish of lens wearers to have a more user friendly disinfection system and the manufacturers responding to that with the introduction of so-called no rub MPS. Added to this manufacturers have reformulated MPS to make them less reactive with the ocular surface (i.e. improve comfort; changing disinfectants and adding “moisturising” agents). From a microbiological and perhaps overall safety point of view, rubbing should be re-introduced as a recommended step in the disinfection of lenses no matter what MPS wearers are using.

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