Volume 81, Issue 8 , Pages 377-380, August 2010
Perils of the “Unstandard” and the habitual hygiene of hydrogels
Article Outline
- Threat of the “Unstandard”
- Enter the fungus, Fusarium
- Enter the protozoan, Acanthamoeba
- Let's rub it out!
- The issue of encystment
- Familiarity can breed contempt
- References
- Copyright
William J. Benjamin, O.D., Ph.D.
This was true despite the absence of any documented case showing that CJD had been communicated from one person to another through the use of contact lenses, the fact that little was known about either prions in general or the spread of CJD in particular, and the limited information about how inactivation of CJD prions could be practically achieved.
Threat of the “Unstandard”
International standardization is a consensus-based process that takes several years to result in a new standard or a substantial change to an existing standard. Gaining agreement from the standards bodies in more than 20 participating countries is not easy. The contact lens subcommittee of the American National Standards Institute (ANSI), an example of only a single of these standards bodies, has more than 30 attending experts representing more than 20 organizations. Agreement is tough to achieve even when much is known about the topic under consideration and no new information is needed from research investigations. It is important that standards be based on credible science.
One of the basic tenets of standardization is that a subject cannot be standardized when it is actually a research project. The CJD prion was a great research project. It still is. Not much was known and there is a lot even yet to discover. But this did not deter some individuals within the regulatory administrations of a few influential countries from insisting that contact lens care standards be written, or substantially modified, on the basis of tenuous assumptions and hearsay. The very existence of entire classes of contact lenses was threatened. Fortunately, cooler heads prevailed on the standards committees, realizing that only a faux consensus could be reached without the basic knowledge necessary to write a legitimate standard. The intensity of pressure for some change in the care standards, any change, eventually began to subside.
It is actually a misuse of the standards organizations to insist that they quickly react in a significant way by creating or modifying standards without adequate knowledge, consensus, or a logical basis to do so. Great havoc can be generated at enormous expense without legitimate reason and, even more importantly, problems can be exacerbated rather than alleviated. The publication of an impractical standard derived in this manner would falsely indicate a high level of confidence in the standard and the integrity of the process through which it was formulated. One might refer to an untenable standard produced in this way as an “Unstandard.” The adverse impact of an “Unstandard” would be compounded greatly by its imposition into law by regulatory bodies in different countries including the United States.
Enter the fungus, Fusarium
Without knowing the underlying cause of what was an uncommon condition, an “Unstandard” was a distinct possibility by reacting too fast, without sufficient knowledge. There could have been a new resistant strain of the genus Fusarium that had become prevalent. Care solutions could have been contaminated with Fusarium, the antimicrobial agent might have degraded over time in bottles on the shelf or after opening, patients might have been noncompliant, or practitioners might have been noncompliant.1 There could have been a reaction between solution ingredients and the new silicone-hydrogel (Si-Hy) lens brands that had appeared on the market, or idiosyncratic corneal staining with certain combinations of Si-Hy materials and care solutions could have been a problem. Any number or combination of factors, some yet to be identified, could have contributed to the Fusarium crisis, and much research and investigation was needed to find out why these Fusarium eye infections were occurring. That was not the time to be writing new standards or substantially altering existing standards to address the Fusarium crisis, when the causes of the problem were likely multifactorial and unknown. Even Global Warming caught an early share of the blame!
The overwhelming majority of Fusarium eye infections in contact lens wearers involved use of a single care product that was taken off the market. Once off the market, the number of Fusarium eye infections reduced to the usual level. Over time a view of the crisis emerged in which Fusarium was able to evade an effective product when tested according to the standards, to which a moisture-retaining ingredient had been added.2 A consensus opinion formed that, with evaporation as can occur when patients “top off” storage cases using only a drop or two of solution,2 the concentration of antimicrobial agent was reduced and a slurry of ingredients precipitated by dehydration collected in the bottoms of lens cases. Fusarium was able to live and multiply inside the semiprotected environment of the slurry, subjected to low antimicrobial concentrations, and was repeatedly transmitted to the eyes of some patients during lens insertion. There is evidence that the new ingredient in this product was absorbed into lenses and potentially reduced the potency of the product during storage in lens cases.3 With repeated exposure to the pathogen, a small number of eyes began to succumb to Fusarium infection. When the number of infections became high enough to recognize over the background level of eye infection, the Fusarium crisis was born.
Having then a consensus opinion regarding the cause of the Fusarium crisis, standards organizations reacted by modification of existing standards to screen out care systems that would produce the scenario related above. At the ANSI and ISO, the requirement for microbial efficacy versus Fusarium and the other 5 challenge organisms was strengthened by making the testing more realistic. The organisms must now be killed or inactivated when growing in an organic substance that makes them hardier, in a manner felt to approach that of the slurry. A test for antimicrobial effectiveness with evaporated solution has been produced. Today, members of the ANSI CL subcommittee are hard at work developing and testing new methods to assure that the potency of care systems are not compromised when used with lenses and lens cases. Thus, the Fusarium crisis or other potential crises related to the postulated causes should not occur once these modifications of the standards are fully adopted. An “Unstandard” was avoided.
Enter the protozoan, Acanthamoeba
Another serious and rare eye infection, caused by Acanthamoeba, increased above the background level of infection while standards organizations were dealing with the Fusarium crisis. Unlike the fungus, Acanthamoeba was a free-living parasite that was not one of the challenge organisms routinely tested with contact lens care systems. Indeed, Acanthamoeba required a greater level of microbiological containment and sophistication to study than existed in the eye care field.
Acanthamoeba has a propensity to infect protected or privileged sites, such as the corneal stroma, and formed hardy cysts when confronted with unfavorable environments such as occur during treatment of the eye or cornea with antibiotic or antiparasitic agents. Thus, Acanthamoebae were difficult to eradicate from the cornea. Though few in number, a single Acanthamoeba infection constituted a sight-threatening, eye-threatening, or sometimes even a life-threatening situation.
The potential for an “Unstandard” was here again a distinct possibility by reacting too fast, without sufficient knowledge of the underlying cause of the infections. There was no proven testing procedure for assessment of the kill of Acanthamoeba by contact lens regimens, and the organism was difficult to work with. The most virulent or resistant species or strains of Acanthamoeba found in eye infections, those which might be best tested against amoebicidal agents, could not be identified. Several variables of the technique involved in assessing kill rates of Acanthamoebae were known to dramatically influence the outcome of amoebicidal comparison tests. There were many other variables of testing that had not yet been examined in scientifically rigorous manners. If ever there was a series of research projects in dire need of investigation that could not be standardized before a host of investigations were carried out, here they were! Yet, the standards organizations ANSI and ISO were pressed to come up with new standards and to promulgate large alterations of existing standards when few of these could be legitimately accomplished by consensus.
More than 50% of the amoebic infections were related to a single product that was removed from the market, but incidents have been identified in which other care systems were used. The background level of ocular Acanthamoeba infections appeared to be on the rise.2 Whether this is real or caused by increased vigilance remains a question. Our ability to identify Acanthamoeba with improved technologies could be another influencing factor. A reduction of water treatment standards in the United States was cited as one reason Acanthamoeba eye infections were becoming more prevalent.4, 5, 6 In Chicago, higher incidence of Acanthamoeba infection was traced to specific areas of the water distribution system.4 Increasing familiarity with Acanthamoeba and its infections among eye care practitioners was felt to be another reason a growing number of cases were being reported.
Let's rub it out!
It was going to take some time for the expertise of working with Acanthamoeba to be acquired in the contact lens field. It would then take considerable time to track down all of the test variables, their influences on the results of amoebicidal agents in contact lens solutions and, if possible, to standardize a test method. Yet major changes to the contact lens standards were strongly advocated without sufficient acumen, necessary research results, or consensus. A considerable effort was made to quickly eliminate “No Rub” from the standards.
Superficially, it makes sense that all patients should rinse and rub their lenses after removal from the eye and before the lenses are placed in their storage cases. Then, when taken out of the lens case for insertion on the eye, contact lenses will be as devoid as possible of microbial and other contamination. Everybody can identify with the need to clean lenses by application of some surface scouring. Beneath the surface, however, the elimination of “No Rub” from all standards became a murky proposition.
Care regimens advertising a “No Rub” capability must pass the standards without a rub step in the procedure. Thus, one might conclude that these regimens are more capable than regimens that can meet the standards only by application of rubbing. If a patient chooses to rub and rinse, then, a better choice from an antimicrobial standpoint could be to select a “No Rub” regimen and actually do the rubbing! In addition, a known area of noncompliance is addressed by regimens that are able to meet the standards without a rub step, for we all know that many patients fail to rub their lenses! To eliminate the ability in all contact lens standards to pass those standards without a rub step could in reality lower the requirements for care regimens rather than increase them!
Fortunately, again, cooler heads prevailed such that “No Rub” wasn't eliminated from the contact lens standards. The issue became one of labeling, in that patients should not be encouraged to dismiss the rub step as they are when the box containers are dominated by the words “No Rub” to entice patients to purchase them. One manufacturer, Abbott Medical Optics, quickly altered its labeling to emphasize “Easy Rub” when the Acanthamoeba outbreak was recognized, to indicate that patients should use the rub step during lens preparation. The standards are now in the process of modification by consensus in the area of labeling of the product—on the box and in the package insert.
Even with these labeling changes, however, is it likely that patients who are noncompliant by not washing their hands before handling their contact lenses will transfer more bioburden to lenses by use of the rub step than without it.7 Debris and some surface accumulation could be removed by rubbing. However, data suggest that, even if one does wash his or her hands, as much bioburden is transferred to lenses by rubbing than would exist on them without rubbing (Mowry-McKee M. Effect of hand washing on bioburden transferred to contact lenses. Unpublished data. October, 2009)!8 Indeed, rubbing/not rubbing was specifically analyzed and not found to have been a statistically significant factor in the Fusarium crisis or Acanthamoeba outbreak!2
The issue of encystment
It was found through research over the last several years that the glycol component of the care product most associated with Acanthamoeba keratitis caused the amoebae to encyst at a much greater frequency than when the amoebae were placed in the care solutions of other regimens. Approximately 25% of the amoebae encysted when placed in the solution removed from the market, whereas most solutions induced less than 2% encystment. One unassociated solution resulted in approximately 8% encystment.9 A theory was logically formulated that cysts could better withstand the procedures and antimicrobial agents intended to prevent Acanthamoeba from reaching the eyes of contact lens wearers. A solution's ability to induce encystment could be a negative factor in controlling contamination of lenses and solutions by Acanthamoeba.
At a symposium held by the U.S. Food and Drug Administration (FDA), sponsored by the American Optometric Association, American Academy of Optometry, American Academy of Ophthalmology, and Contact Lens Association of Ophthalmologists, experts reached a consensus that encystment could be an important feature of the outbreak.10, 11 The ANSI contact lens subcommittee and the ISO contact lens working group are generating a screening test for Acanthamoeba encystment that could identify care regimens that induce high levels of encystment. The test should be ready by the time more information credibly establishes a link between high levels of encystment and Acanthamoeba keratitis. Should the link not be established, or even discredited, the encystment protocol can be abandoned. Such is the problem of standardizing a “moving target,” something that is actually a research project.
Familiarity can breed contempt
Great strides in the effectiveness of contact lenses and contact lens care regimens were made over the last 25 years, when antimicrobial efficacy was balanced against ocular toxicity and allergic reactions.12 Practitioners, patients, manufacturers, and regulatory agencies have become more knowledgeable about the capabilities of lenses and care systems as they have minimized the combination of allergic, toxic, and infective incidents.
Yet the frequency of eye infections during contact lens wear has remained fairly consistent to the present day or even may have increased. In my view, one big factor not generally recognized is that, as lenses and regimens have trended the wear of contact lenses more innocuous, practitioners and patients have compensated to attenuate the benefits of the strides that have been made. Lenses are worn longer, with less emphasis on hygiene, by more of the population including “the fringe” of what might be considered excellent candidates for contact lens wear. Contact lenses are treated more and more as commodities instead of medical devices. They are worn through colds and the flu, too often overnight, sometimes without hand washing after topping off the solutions in polluted lens storage cases, and are shared between individuals especially during the Halloween season. Even the government concluded that tap water was so safe that water treatment standards in the United States could be relaxed.4, 5 Thus, it appears, we must all go back to the fundamentals and become more fastidious if we really intend to lessen the frequency and severity of infectious problems associated with contact lens wear.
References
- Stone R. The Importance of Compliance: Focusing on the Key Steps. Poster presented at the meeting of the British Contact Lens Association, Burnaby, UK, April 21, 2007.
- National outbreak of Acanthamoeba keratitis associated with use of a contact lens solution, United States. Emerg Infect Dis. 2009;15(8):1236–1242
- Biocide uptake in contact lenses and loss of fungicidal activity during storage of contact lenses. Eye & Contact Lens. 2006;32(6):262–266
- Epidemiological characteristics of a Chicago-area Acanthamoeba keratitis outbreak. Am J Ophthalmol. 2006;142(2):212–217
- U.S. Environmental Protection Agency. Stage 1 disinfectants and disinfection byproducts rule. Vol EPA 815-F-98–010 Washington: Environmental Protection Agency; 1998. Available at www.epa.gov/safewater/mdbp/dbp1. Last accessed March 22, 2010.
- Shifting distribution of Chicago-area Acanthamoeba keratitis cases. Arch Ophthalmol. 2010;128(1):137–139
- . Microbial contamination of contact lenses, lens care solutions, and their accessories: a literature review. Eye & Contact Lens. 2010;36(2):116–129
- . Microbial contamination of contact lenses, part II: quantitation of microbes after patient handling and after aseptic removal from the eye. J Contact Lens Assoc Ophthalmol. 1992;18:240–244
- Encystment of acanthamoeba during incubation in multipurpose contact lens disinfectant solutions and experimental formulations. Eye & Contact Lens. 2008;34(3):133–139
- U.S. Food and Drug Administration. Summary of January 22 and 23, 2009 Microbiological Testing of Contact Lens Care Products Workshop. U.S. Food and Drug Administration Workshop on Microbial Testing of Contact Lens Care Products, Silver Spring, MD, January 22-23, 2009; Available at: www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences. Last accessed March 22, 2010.
- Benjamin WJ, Bennett ES, Sindt CW, et al. Combined Closing Statement of the American Optometric Association and American Academy of Optometry. U.S. Food and Drug Administration Workshop on Microbial Testing of Contact Lens Care Products, Silver Spring, MD, January 23, 2009; Available at www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences. Last accessed March 22, 2010.
- . Review of standard for evaluating the effectiveness of contact lens disinfectants. PDA Journal of Pharmaceutical Science and Technology. 2002;56(1):37–50
William J. Benjamin, O.D., Ph.D., is a Professor of Optometry and Vision Science at the School of Optometry, University of Alabama at Birmingham. A former chair of the American Optometric Association’s Commission on Ophthalmic Standards, he recently received the “Statesmanship Award” from the contact lens working group of the International Organization for Standardization and was cited for his impartiality and leadership in convening this group over the 15 years from 1994 to 2009. He has garnered research contracts from many of the contact lens and solution manufacturers as a part of his scholarly duties at the university and is currently an expert witness for J&J/Vistakon, Inc.
PII: S1529-1839(10)00271-X
doi:10.1016/j.optm.2010.05.001
© 2010 Published by Elsevier Inc.
Volume 81, Issue 8 , Pages 377-380, August 2010
