How Dangerous is Noncompliance with Multipurpose Solutions?

Thomas Tsai, A.B.O.C., E.N.A.O. and H. Kathleen Dannelly, Ph.D.
JANUARY 2000

Learn about the efficacy of common MPSs against patient non-compliance. You might be surprised by the findings of this experiment.

Pseudomonas aeruginosa has emerged as a significant threat to contact lens wearers, especially extended-wear contact lens wearers. The organism has been observed to initiate an infection of the cornea in a matter of hours and can quickly lead to vision impairment and blindness.

Methodology

Using an animal model for corneal infection, we have observed that blindness can occur within 36 hours when P. aeruginosa is left untreated.

When P. aeruginosa is grown in rich media in the laboratory, it has a doubling time of approximately 45 minutes. Therefore, it's possible that it can double in number in the patient's eye in less than an hour; one hour passes and 1000 cells multiply to 2000, another hour passes and 2000 cells multiply to 4000, etc.

Where To Look

P. aeruginosa can be found virtually everywhere. It's a normal inhabitant of the soil, and is well-known for its ability to survive in almost any moist environment. It has even been observed to grow on hand soap and in mild antiseptics. It is normally considered an opportunistic pathogen, commonly infecting people who are otherwise debilitated by cystic fibrosis, Acquired Immunodeficiency Syndrome (AIDS), burn, chronic lung disease and other immuno-compromised patients.

An Increase In Infection

Eye infections due to P. aeruginosa were very rare before the use of contact lenses. The use of extended-wear has caused this infection to become a more common threat. Although the conditions for infection have not yet been fully elucidated, it appears that changes on the surface of the eye during contact lens use allow the initiation of the infection. The best evidence for this requirement is the fact that to set up the infection in an animal model, the eye must first be injured. Merely adding virulent P. aeruginosa to a healthy eye will not cause infection.

Purpose

Multipurpose contact lens solutions ease the daily routine for the contact lens wearer. The instructions for using these products include washing one's hands and rubbing the lens with the multipurpose solution for 10 seconds, followed by rinsing and soaking the lens in the solution for at least four hours.

The regimen for proper use of these solutions is greatly simplified in comparison to the traditional regimens, including multiple-step regimens, enzyme treatments, etc.

However, having the patient understand and follow the important routine for using multipurpose solutions is an issue of concern. The patient's education about compliance is often incomplete, and the manufacturer's recommendations are often forgotten or overlooked.

When the routine overshadows the importance of the regimen and the patient becomes lax in their diligence, what are the consequences?

Experiments

We tested five common multipurpose contact lens solutions against two strains of P. aeruginosa that were isolated from the patients' eyes.

These strains are especially equipped to cause severe ocular infections. For example, one strain is an intracellular pathogen, meaning that it enters the corneal epithelial cells during the infection process. This is an especially tough infection to treat because antibiotics, such as aminoglycosides, which do not enter the epithelial cells, cannot work. The organisms avoid the antibiotics, as well as humoral immune factors, such as antibodies, by hiding out in the cells. The other strain is strictly an extracellular pathogen, which means it's easier to treat, but produces toxins, thus causing much cellular damage.

We tested the multipurpose solutions by suspending the organism at a concentration of 10 million cells (1x10⁷) per milliliter of solution, and incubating it for a total of eight hours at room temperature. We then collected results by removing samples and counting the bacteria present using routine plate count methods at zero, four and eight hours incubation at room temperature.

The U.S. Food and Drug Administration (FDA) guidelines for multipurpose contact lens solutions require a three-log unit reduction in the number of bacteria to be on the market. Our results are presented as the log of the cell number. (For example: 1,000,000 or 1 x 10⁶ bacteria are equal to a log of 6.0. To calculate log reduction, subtract the four or eight-hour time point from the zero time point.)

Differences

There are two major differences between our experiments and those required by the FDA. First, we started with approximately 10 times more viable cells than what is required, and second, we used patient isolates rather than stock strains.

Because a three-log reduction in the number of cells indicates that the solution is working, our results are comparable to those obtained using FDA standards, except that they are even more stringent since we require that the solutions work with higher starting concentrations.

Also, it's important to note that 1 x 10⁷ cells is a feasible concentration that could easily be attained in an eye infection. Stock strains are organisms that have been passed on artificial media for many generations, and often, these organisms lose their disease producing ability.

Our data may provide a more accurate picture of how the lens care solutions work with virulent, pathogenic organisms that are isolated from patients with eye infections.

Results

The five solutions tested were Opti-Free Express Enhanced Disinfection Formula (Alcon), Opti-One Solution (Alcon), Opti-Free Express Multi-Purpose Solution (Alcon), ReNu MultiPlus Solution (Bausch & Lomb) and Complete Brand Multi-Purpose Solution (Allergan).

All solutions resulted in the kill rate required by the FDA except ReNu MultiPlus solution. ReNu required eight hours to achieve its goal with the intracellular P. aeruginosa and did not result in a three-log reduction with the extracellular organism even after eight hours of incubation.

Opti-One solution gave the required three-log reduction in four hours, but was significantly more effective with the extracellular P. aeruginosa after eight hours (Table 2). The same was true for Opti-Free Express Multi-Purpose solution with the intracellular P. aeruginosa (Table 1). In these two cases, it would be beneficial to have the patient soak their contact lenses overnight. However, in all other cases there was not a significant difference between four and eight hours of incubation.

Conclusions

In our tests, Opti-Free Enhanced solution was by far the best disinfectant. On contact, it reduced the number of intracellular organisms by four orders of magnitude and reduced the extracellular by five orders of magnitude within four hours of incubation.

It was also clear from our experiments that there are differences in the two patient strains of P. aeruginosa and how they respond to the different multipurpose solutions.

It's possible that different results would have been obtained if we had used the stock strains of P. aeruginosa, since they are probably not as virulent or as resistant to disinfectants after passing them on artificial media numerous times.

Future Work

The next question we would like to answer is: "Will the solutions work if the bacteria are not free-living, but are found as a biofilm on lenses?" This would probably provide a more accurate picture of how bacteria occur on the contact lens after patient use. We are preparing to investigate this question in our next article.

We would like to thank Dr. Suzanne M. J. Fleiszig at the University of California at Berkley for supplying the patient strains used in these experiments.

Mr. Tsai is an optician and a full-time student at indiana state university, majoring in both life science and chemistry.

Dr. Dannelly is assistant professor of life sciences at indiana state university.