CARE SOLUTION REGULATION

Testing Care Solutions: Need for Evolution

It may be time to update the regulations associated with testing contact lens care solutions.

By James Lonnen, PhD

Dr. Lonnen is director of the Amoebae Laboratory in the Department of Infection, Immunity and Inflammation at the University of Leicester, UK. He has worked with AMO, Bausch + Lomb Inc., Johnson & Johnson Vision Care, Inc., Menicon Co. Ltd., and Sauflon Pharmaceuticals Ltd.

Contact lens disinfectant solutions are controlled and tested against international standards of efficacy. To go to market, they must exhibit sufficient disinfection efficacy against a range of microorganisms.

Even so, manufacturing companies recognize that a number of important ocular pathogens are not included in the regulatory standards, and therefore they often conduct additional testing. However, there currently are no standardized methods for evaluating disinfectants against some of these additional pathogens, resulting in variable results. While formulations of contact lens disinfectants are improving, it may be time to update the regulatory standards.

Contamination Happens

There are currently estimated to be at least 125 million contact lens wearers across the world (Barr, 2005), and most people experience few complications; however, contact lens wear is recognized as being a significant risk factor for the development of microbial keratitis (Dart et al, 1991; Bourcier et al, 2003). Due to the ubiquitous distribution of microorganisms, it is extremely difficult to prevent them from colonizing contact lens storage cases, especially because lens cases are moist environments that are frequently inoculated with organic material by users. Microbial contamination and biofilm formation in contact lens cases is therefore common—even in compliant lens wearers. Microorganisms that grow within biofilm have been shown to be more resistant to antimicrobial agents compared to planktonic microbes, as the glycocalyx matrix that makes up the biofilm offers protection to the organisms within (Elder et al, 1995; McLaughlin-Borlace et al, 1998).

Bacteria, fungi, and amoebae have all been found in contact lens cases. These can adhere to the contact lenses, which then act as a vector to transport the microbes onto the surface of the eye (Gray et al, 1995; Kilvington and Larkin, 1990). Also, the ocular surface trauma and hypoxic conditions that are caused by contact lens wear enable pathogenic microbes to adhere to the cornea, therefore increasing the risk of infectious keratitis (Imayasu et al, 1994; Liesegang, 1997).

Current Regulations

Current requirements for contact lens care solutions to fulfill the European ISO and the U.S. Food and Drug Administration (FDA) standards include, along with other assays, disinfection efficacy according to ISO 14729 (International Organization for Standardization, 2001). This includes standard strains of five microorganisms: three bacteria and two fungi, which historically are known to cause eye infections.

Clinical Isolates

However, companies and key industry opinion leaders are realizing the importance of updating these testing requirements. Microorganisms, in particular bacteria, can evolve extremely quickly, so it is therefore important to test lens care solutions against a range of microorganisms that are representative of those that have recently caused disease in humans, such as recent patient clinical isolates. Clinical isolates are pathogens that have been isolated from a clinical case of disease and have not been passaged in the laboratory. As microbes evolve rapidly and can easily acquire and discard DNA in accordance with their current needs, if they are serially passaged in a laboratory, they will potentially lose their virulence and drug resistance genes and therefore become very different to how they were when causing disease in the human body.

Clinical isolates can also vary from region to region, which is an important consideration for contact lens care solution manufacturers who produce one product and then sell it globally. While it may not be feasible to test clinical microbes from every region, experts seem to be in favor of including clinical isolates from at least two or three key global regions along with the standard strains. Some companies are already testing against clinical isolates, resulting in the selection of more effective contact lens disinfectants. However, lack of regulatory oversight means that the strains chosen for these studies do vary, producing inconsistent results.

Recently, talks have begun on the topic of testing contact lens disinfectants against a broad range of clinical isolates. While logistically it would be impossible to test them all, inclusion of a panel of carefully selected clinical isolates that are representative of key ocular pathogens from different global regions would be sufficiently more rigorous as compared to the current standards and therefore should result in the development of more effective care solutions.

Results of a recent study titled “Efficacy of contact lens care solutions against clinical microorganisms” concluded that while the care solutions tested showed broad-spectrum efficacy against a range of pathogenic and antibiotic-resistant clinical isolates, certain formulations did show lower activity against certain bacteria and fungi such as Staphylococcus aureus, Enterococcus sp., and Candida sp. (Heaselgrave et al, 2011) (Table 1). There was also significant variation in efficacy against lens storage case isolates. This study indicated that certain multipurpose lens care solutions may select for the growth of inherently resistant bacteria in lens storage cases, resulting in the presence of organisms capable of causing keratitis, including Acanthamoeba, and a significant microbial burden that could elicit an inflammatory response resulting in corneal infiltrates or sterile ulcers.

Other Pathogens

Another important ocular pathogen that is found in contact lens cases but is not currently recommended for testing in the regulatory standards is Acanthamoeba. This free-living amoeba is commonly found in dust, soil, rivers, ponds, and even air-conditioning systems and domestic tap water. It is an opportunistic pathogen that, while rare, can cause a painful and potentially blinding keratitis, which is very difficult to treat. People who wear contact lenses are most at risk of developing Acanthamoeba keratitis, and studies have shown that approximately 90 percent of patients who've had this type of keratitis were contact lens wearers (Radford et al, 1998).

The number of contact lens wearers worldwide is increasing every year, as are the numbers of cases of infectious eye disease, in particular from emerging pathogens such as Acanthamoeba. This is driving manufacturers to test beyond the standard microbial strains. While efficacy against Acanthamoeba is not required in the current regulatory standards, most companies recognize that it is an important ocular pathogen and have independently started testing their disinfectants against this microorganism. However, as the test methods for the evaluation of contact lens disinfectant solutions against Acanthamoeba are yet to be standardized, the results of assays undertaken in different institutions often vary.

Another criterion not included in the current regulatory standards is assessment of the disinfection efficacy of evaporated lens care solutions. While some care solutions maintain efficacy when dried down to half their original volume, others have a significant reduction in efficacy (Kilvington et al, 2011). Also, studies have shown that drying residues of some multipurpose solutions on contact lens cases may induce and harbor resistant forms of infectious microorganisms (Ahearn et al, 2011). Therefore, if lens wearers leave the caps of their lens cases off or loose or if they reuse or “top off” the care solution rather than fully discarding and refilling with fresh solution, this could increase the risk of eye infection, especially in warmer countries.

Hygiene and Compliance

Eye infection usually results from poor lens and lens case hygiene practices such as failing to comply with the recommended disinfection routine; other risk factors include not washing the hands when applying and removing lenses and using tap water or homemade saline to wash and store lenses. In addition, swimming or showering while wearing lenses is not recommended. It's extremely important to follow the instructions on care solution bottles because what appears there is the regimen that was tested and proven efficacious in the laboratory. The regulatory standards need to be improved, but a key factor is to improve patient compliance.

Over the last few years, the strong recommendation has been to rub and rinse contact lenses with the lens care solution before soaking them. Just soaking lenses in the disinfectant solution does not provide the mechanical removal of the microbes, so key opinion leaders now recommend that patients rub their lenses well in the palm of their hand with their finger and a few drops of care solution, rinse the lenses, and then soak them for the recommended time.

Also, it is recommended to change cases regularly—approximately once per month. New cases are often supplied with bottles of care solution, eliminating any excuse for not changing the case frequently.

Conclusion

The contact lens care solution industry has learned a number of valuable lessons in the last few years regarding emerging pathogens, clinical isolates, evaporation of solutions, and overall risks inherent with lens cases. While they have independently started testing these additional factors and are continually improving their disinfectants, there is still much debate on the consistency of the testing and the final outcome. Now may be the time for the governing bodies to update the regulations and standardize the testing to further protect consumers. CLS

For references, please visit www.clspectrum.com/references.asp and click on document #201.