What is the Solution?
Posted by
Armand RossettiJuly 06, 2007 9:42 AMMost strains of Acanthamoeba will survive exposure to AMO's Complete MoisturePlus, Alcon's OptiFree Express and B&L's ReNu MultiPlus. Under testing conditions that reflect the "real world," none of those solutions are stellar performers, and only one is effective under certain conditions.
Recently, Complete Moisture Plus has been shown to be seven times more likely to have caused the most recent contact lens related Acanthamoeba outbreak, but just how much less effective is AMO's Complete than B&L's ReNu MultiPlus or Alcon's OptiFree Express solution?
Although Acanthamoeba keratitis (AK) is not a new phenomenon, it is a fairly recent one. The first AK cases were recognized in 1973. However, before soft contact-lens wear became popular, AK was extremely rare. As soft hydrogel lenses became more prevalent, exposure to Acanthamoeba led to an epidemic that began in the early 1980s, and the number of AK cases increased dramatically beginning in 1984.
By 1985, investigators had established a connection between AK infections and the use of contact lenses. As early as 1987 further studies revealed that AK occurred more commonly among men, as well as in contact-lens wearers who failed to disinfect their lenses as frequently as recommended, swam while wearing lenses, or used homemade instead of commercially prepared saline solution.
In January 1997, the CDC conducted a retrospective survey of 22 ophthalmology centers across the United States to determine whether the infection rate was increasing nationwide. By March 2007, the CDC had determined the existence of widespread, culture confirmed cases of AK, and that the most recent increase in cases had begun in 2004 and continued through 2007.
On March 16, 2007, the CDC began a multistate investigation to look for AK related risk factors. It was at this time that use of AMO's Complete MoisturePlus emerged as being most closely connected with the latest rise in contact lens related AK.
The most recent increase in the number of contact lens related AK cases raises certain questions: Why has this phenomenon occurred? Why is AMO's Complete MoisturePlus mostly to blame? Are other no-rub solutions connected with the outbreak, and to what extent? Is there anything that can be done to alleviate the AK problem?
Although the foregoing questions are broad, open ended, and cannot be answered without substantial investigation (certainly not in a blog), consider the following observations:
NOT ONE, SINGLE NO-RUB SOLUTION CAN CLAIM TRUE EFFICACY IN COMBATING AK, AND OF THREE NO-RUB SOLUTIONS RECENTLY TESTED, COMPLETE MOISTUREPLUS PLACED LAST
In its March 2007 edition, Optometry and Vision Science contained an article by Megan Shoff, et al. The Shoff article compared the variable responses of 14 different Acanthamoeba strains to three no-rub solutions, namely, MultiPlus (B&L), Complete (AMO, a spin off of Allergan) and OptiFree Express (Alcon). The investigators subjected each of the two sets of 14 strains to each of the three solutions to test survival rates at 3, 6, and 24 hours of exposure. One set was Acanthamoebae in the more vulnerable trophozoite stage, and the other set was Acanthamoebae in the much less vulnerable encapsulated cystic stage. The results were surprising.
According to graphs contained in the study, over 90% of exposed trophozoite Acanthamoeba withstood a 3 hour and 6 hour exposure to AMO's Complete (a less than 10% kill rate). ReNu was able to achieve only 12% in three hours and 14% in 6 hours. OptiFree was the stellar performer under these testing conditions, with a 31% kill in 3 hours and 42% in 6 hours. It took a 24 hour exposure for Complete to approximate a less than efficacious 6 hour exposure to ReNu MultiPlus.
Turning to the cystiform Acanthamoeba results, It took a 24 hour exposure for Complete to achieve an approximate two (2) % kill; this was a very poor result. The best that OptiFree could achieve was 18% kill in 24 hours (not 3 or 6 hours). Three and six hour exposure using Complete resulted in zero (0) % kill. Complete's performance contrasted with an equally paltry 2 - 7% kill range for ReNu MultiPlus and OptiFree Express. The results speak for themselves, but let's play fair and analyze the testing methods.
SOLUTION MANUFACTURERS HAVE USED EFFICACY TESTING THAT HAS NOT ACCURATELY REFLECTED "REAL WORLD" AK INFECTION FACTORS
The method that most manufacturers use to report their results is based on the decimal kill rate. Manufacturers will defer to the FDA, indicating that log reduction is the gold standard for testing. Until the advent of one step solutions, that may have been the case. However, solution manufacturers are considered experts in the field of eye care. And as experts, manufacturers may have to transcend and/or educate regulatory agencies that a different approach to testing solution efficacy might be necessary. For example, the Shoff study has used the 100% inactivation method, which purportedly had the following advantages over log reduction:
1. The method was rapid and allowed for a screening of a wider range of strains.
2. The investigators were able to separate the trophozoites from the cysts, yielding more accurate and comparative analyses. Inadvertently including cyst forms with trophozoites could seriously undermine experimental results.
3. The test actually mimicked the response to Acanthamoeba attached to a surface (which would better represent microbial attachment to contaminated contact lenses). Acanthamoebae colonizing a contact lens are buried in biofilm that might afford better protection from cleaning solutions.
4. The present testing method did not disturb cells by centrifuging or vortexing them. For example, centrifugation might not affect the survival of cysts, but might damage sensitive trophozoites.
5. The Acanthamoebae were not starved. They were tested while growing on bacteria, making them more challenging, which is more "real world."
In addition, the Shoff study was able to show that testing axenically cultured strains of Acanthamoeba, the way that manufacturers usually do, has two important limitations:
1. The axenic strains are selected in the laboratory and may not represent the "hardiness' of bacterized wild strains.
2. It is likely that Acanthamoeba on contact lenses are surviving in the biofilm on the lens surface, where you can find components such as; tear film, proteins, mucins, lipids and bacteria. This is a very different environment than is found in a "squeaky clean" axenic system.
The Shoff study also restated the truism that some strains of Acanthamoeba are harder to kill than others, and that it would be prudent to choose a harder strain of Acanthamoeba, before undertaking solution sensitivity testing.
As previously mentioned, older testing methods do not mirror actual contact lens wearing conditions. The Shoff study has stated that the inability to kill more than 20% of any strain of Acanthamoeba is disturbing. This important observation should foster the necessary research to find more effective and less toxic chemical disinfectants or to encourage an effort to formulate more effective solutions. The Shoff study sould also lead authorities to question the validity of current axenic testing methods, and to find acceptable alternative methods.
For more information on this subject, please refer to our section on Defective and Dangerous Products.