Two Questions that Concern AMO and Acanthamoeba Infections
Posted by
Armand RossettiJune 12, 2007 2:24 PMThe cornea is the only tissue in the body that Acanthamoebae (or Acanthamoeba) can invade in individuals with healthy immune systems. Otherwise, those individuals can usually avoid Acanthamoeba infections that affect the skin, brain and lungs. This blog briefly addresses two questions: 1) Why is the cornea more susceptible to Acanthamoeba than other tissues in the body; and 2) How could a multipurpose disinfectant solution, such as AMO's Complete MoisturePLUS aid in promoting Acanthamoeba infection?
Question 1:
How does Acanthamoeba invade corneal tissue?
Acanthamoeba is everywhere; it is found in water fountains, tap water, bottled water, freshwater ponds, thermal water, well water, Jacuzzis, swimming pools, aquaria, municipal sewage, ocean sewage, house dust, garden soil, sand boxes, garden vegetables, fish and air conditioners. This list is not exhaustive. Conventional treatment of water delivery systems will not necessarily kill all Acanthamoeba.
The answer to why Acanthamoeba has an easier time infecting the cornea seems to be connected with certain chemicals found on Acanthamoeba's outer membrane, one of which is called mannose binding protein (MBP). Researchers have long suspected and now have proof that MBP allows Acanthamoeba to bind to corneal cells.
Despite having help from MBP, however, Acanthamoeba usually have trouble binding to corneal tissue. This difficulty is evident because the eye has a natural defense mechanism found in tear film. Tears are usually loaded with beneficial chemicals, enzymes and antibodies that have complicated names, such as lysozyme, lactoferrin, and secretory IGA. In addition if you are normally healthy, just blinking your eye can protect you against Acanthamoeba infection. It may not seem obvious at first, but blinking increases the tear fluid volume that contains those Acanthamoeba fighting chemicals.
However, once Acanthamoeba overcomes the natural defense system and chemically sticks itself to the cornea, Acanthamoeba can begin to mount its own insidious chemical attack on the cornea. This Acanthamoeba attack is called a cytopathic effect (CPE), and that process leads to a systematic destruction of targeted corneal cells. Furthermore, if Acanthamoeba can gain a foothold on the cornea, and can use bacteria that are present as a food source.
To make matters worse, contact lenses can serve as vectors. A vector is a means of transmitting an infective agent from one location to another. In the case of Acanthamoeba keratitis, the contact lens, itself, can transport amoeba found in many locations, including contact lens cases, to the eye. Even if a lens case is Acanthamoeba free, a lens, coated with lens solution, containing chemicals that create a "friendly" environment for Acanthamoeba to thrive, can attract Acanthamoeba from almost anywhere in the environment.
It is also interesting that Acanthamoeba can live symbiotically with bacteria. Living symbiotically means that Acanthamoeba have the uncanny ability to "eat" some bacteria for nourishment, and process other bacteria through its system to create stronger, more virulent bacterial strains. Acanthamoeba can then deposit the more virulent processed bacteria on the corneal surface. Those bacteria then act as Acanthamoeba's "allies," mixing with tear fluid and weakening the cornea's natural resistance to all microorganisms, including Acanthamoeba. The enhanced organisms then continue to multiply, playing havoc relentlessly with the eye's chemical defense system.
Question 2:
What role did AMO's one step "no rub" solution, Complete MoisturePLUS, play in causing the recently reported Acanthamoeba outbreak?
The CDC estimated the risk of Acanthamoeba infection as being at least seven times greater for those who used Complete® MoisturePLUSTM solution versus those who used other solutions.
Let's start by looking at the mechanical and chemical aspects of corneal keratitis. It is well known that microtrauma to the cornea increases Acanthamoeba's opportunity to invade corneal tissue. Trauma also enhances the ability of most other organisms to attach themselves to or to otherwise infect the cornea.
Microtrauma causes tiny sores to appear as scratches or openings on the cornea's otherwise tough and impermeable surface. Microtrauma can occur as a result wearing ill-fitting contact lenses, from using multipurpose solutions that might be toxic to the cornea, from using incompatible contact lens-lens solution systems, or from a combination of all three plus other factors.
In addition to microtrauma, a biochemical imbalance caused by the presence of wear-contaminated multipurpose solution could disrupt the eye's defense mechanism. Stubborn, hard to remove solution components that remain on the lens, even after soaking, can lower the concentration of antibodies that would ordinarily combat Acanthamoeba's attempt to attach to and infect the cornea. Let's take a look at ingredients found in one-step solutions that might be contributing to biologically enhanced "chemo trauma."
For example, let's look at some of the ingredients found in Complete MoisturePLUS. In addition to other chemicals, Complete MoisturePlus contains hydroxypropyl methylcellulose and propylene glycol that serve as lubricants and Poloxamer 237 a "slippery" component (surfactant). Experts, including manufacturers who are always regarded as experts in their field, should be focused on whether remnants of one or all of these ingredients on used lenses are impossible to eliminate from the lens surface without rubbing.
If rubbing is necessary, a soaking only procedure would cause cumulative contamination of the cornea/contact lens/solution environment. Experts should also focus on: 1) whether any chemical components can cause chemical microtrauma; and 2) whether the Poloxamer 237, which itself is a reverse hydrogel, can react with the lens hydrogel to challenge the solution's disinfecting capability.
Perhaps one major reason for the Acanthamoeba outbreak has been the "no rub" obsession.
Certain one step solutions, which have been loosely advertised as "no rub" disinfecting solutions do not adequately clean contact lenses without rubbing. In the pursuit of market share, manufacturers have diminished the importance rubbing lenses for only a few seconds to eliminate stuck on contamination and rinsing them before soaking. It is a dangerous practice to deliberately downplay the importance of rubbing just to make a marketing point.
In fact, more than one manufacturer has been irresponsible in pursuit of glib marketing. As all manufacturers know or should know, most one step solutions may react unpredictably when used with the hundreds of different types of soft lenses on the market today. Manufacturers have not tested their solutions with each type of lens. Therefore, manufacturers should not have advertised, generally, that no rub solutions were cabable of cleaning all types of lenses. Manufacturers' failure to exercise more care before making such claims could be a major factor resulting in abnormal incidents of Acanthamoeba keratitis.
It makes sense, as well, that carrying polluted lens surfaces from the eye to the lens case for soaking, without first rubbing the sticky, contaminated remaining solution off the lens surface could endanger the delicate ocular environment.
In addition, it should have made scientific sense to manufacturers that failing to take a few seconds to rub lenses clean before soaking them was as bad a practice, if not a worse practice, than topping off lens solution in a lens case. Manufacturers should have realized (and probably did realize from the get go) the need to rub lenses when using a so called "no rub" solutions.
Rushing to be first in the marketplace of ideas in order to capture market share is no excuse for being careless.
What time and resources would manufacturers have had to expend to run tests to compare rubbing to no rubbing using consumer test groups? Methods for such testing had appeared in Optometry and Vision Science several years ago, together with a warning about the need for further no rub testing. Yet, manufacturers chose instead to release solutions without first conducting proper testing.
Recently, Bausch & Lomb's Director of Professional Relations, Dr. Christopher Snyder, recommended rubbing contact lenses before soaking them in ReNu MultiPlus multipurpose "no rub" disinfecting solution. In listening to Dr. Snyder's words, the message is clear. There is no such thing a totally effective "no rub" solution. Dr. Snyder has also expressed the long realized importance of rubbing lenses a second time, in Bausch & Lomb's Special Report, a Supplement to Contact Lens Spectrum.
More than three years ago, manufacturers such as AMO and Bausch & Lomb had ample opportunity to avoid grave danger to the public, and could have done so by admitting just how inadequate all one step "No rub" solutions were in fighting a wide spectrum of opportunistic corneal infection. The manufacturers could have at least alerted providers.
Knowledgeable providers usually instruct their patients not to top off solution in a lens case. Therefore consumers that are so instructed, become knowledgeable and must take some responsibility for their own actions for failure to follow instructions. However, by using slick advertising, manufactures continuously advised providers, whether sitting at roundtables, reading journals or taking continuing education classes, that one-step solutions were effective "no rub" solutions.
Therefore, those trusting providers had no reason to instruct their patients to perform effective lens hygiene by rubbing their lenses before soaking. Patients who were not properly instructed or warned cannot be held responsible for "bad hygiene practices."
Likewise, if patients are continuously bombarded with media advertising that portrays a lens solution as a breakthrough, one step, "no rub" solution, those consumers will not question the veracity of that statement, or discuss it with their providers. And the "no rub" advertising mantra then becomes gospel to consumers. Unwary providers add legitimacy to such advertising claims by unknowingly reinforcing manufacturer's untested misrepresentations, and handing out solution trial packs to their patients.
Early on, all one step "no rub" manufacturers should have done what Dr. Snyder is now doing...telling the truth. It is better to be tardy with the truth, than not following through at all in an effort to run for cover.
Lastly, as the FDA has found, and AMO has admitted by its recall, something is unreasonably dangerous about AMO's Complete MoisturePLUS. Manufacturers like AMO are in the best position to determine the reasons for that danger. Furthermore, AMO has had a duty for more than a year, to warn consumers and providers about that danger. As a result of not warning of the danger, AMO now has an obligation to compensate affected consumers for injuries that Complete® MoisturePLUS has caused.
It is time for AMO and other manufacturers in a like position to step up to the plate, before it's too late. A little manufacturer concern is worth a lot of consumer pain, injury and frustration.