Advancing Clinical Knowledge
Practitioners are learning more about how bioburden threatens ocular health and contact lens comfort.
Dr. Szczotka-Flynn: In general, we think of micro-organisms in three stages (Stapleton, 1993; Behlau, 2008; Elder, 1995). The first is a planktonic phase, in which the organisms are free-floating cells. Second, there's an aggregation and initial adherence phase when microorganisms loosely attach to the lens or the case. Virulence in this phase is similar to the planktonic phase and, like the planktonic phase, it is usually reversible. We can detach the organism from the lens or the case. This is then followed by irreversible attachment.
The third phase is biofilm. After an organism attaches to the plastic lens or case, it shifts its genotype and phenotype, causing it to begin secreting an extracellular matrix and multiplying within that matrix. Biofilms form within 30 minutes of the attachment phase, but this phase is irreversible. In the biofilm phase, the organisms have changed to become more resistant to the host's immune system, disinfectants, antibiotics and other threats. This is their survival mechanism. Most times, biofilms are invisible to the naked eye.
Dr. Potter: How have changes in solutions and materials technologies affected the biofilms you're seeing?
Dr. Szczotka-Flynn: Well, a couple of things influence biofilm formation. For example, certain bacteria often adhere to more hydrophobic and drier surfaces but it depends on the substrate (Patel, 2003). So, in theory, certain hydrophobic lenses may bind more biofilm. Conversely, we've seen solutions that enhance the wettability of the lens surface (Meadows, 2005). A less “sticky” surface may decrease the likelihood of biofilm formation. Of course, the disinfecting properties of solutions are even more important in their ability to limit biofilms.
BIOFILMS AND COMPLIANCE
Dr. Potter: Do specific compliance behaviors affect this problem?
Dr. Szczotka-Flynn: Compliance is a huge factor in biofilm formation. A non-compliant patient who doesn't change his case regularly will have a much denser biofilm to overcome.
As an example, peroxide has been shown to be very effective against biofilms (Szczotka-Flynn, Cornea, 2009). But if patients are non-compliant with peroxide and they top it off or just leave their lenses in the neutralized non-preserved saline for a prolonged period, there is tremendous risk for surviving organisms to proliferate into a biofilm. Peroxide systems are very effective against biofilms when used properly, but if they're not used properly, you can have a worse scenario than any that are possible with multipurpose systems that have continuous disinfection in the case.
Dr. Brujic: That's a very good point. I think as eyecare practitioners, we tend to think about patients topping off multipurpose solutions, and we don't think about patients topping off with peroxide solution. We need to be aware that topping off peroxide-based solutions is a compliance problem that can potentially decrease the efficacy of this disinfecting system.
Dr. Potter: Since the biofilm can be attached to the case, should patients be mechanically rubbing their lens cases?
Dr. Szczotka-Flynn: Yes, that's very important. Biofilms are firmly attached to the surface, but they can be dislodged with mechanical pressure. Mechanical rubbing of the lens case is an additive option to remove more biofilm than just rinsing or drying it.
RISK OF INFECTION
Dr. Potter: What's the most common adverse event associated with biofilms?
Dr. Szczotka-Flynn: Infection is the most serious adverse event (Elder, 1995; Khardori, 1995; McLaughlin-Borlace, 1998; Stapleton, 1995; Zegans, 2002; Zegans, 2005). Infection is what we fear the most, and a biofilm-associated infection is likely more difficult to control than other microbial keratitis we see.
Not all bacteria (or fungi) form biofilms, and biofilms are usually polymicrobial, containing several species. Interestingly, most of the clinical isolates of Fusarium keratitis that were gathered by the CDC in the Fusarium keratitis outbreak do form biofilm (Szczotka-Flynn; personal communication). However, the Fusarium specified in FDA and ISO testing is a very weak strain that does not form biofilm (Imamura, 2008).
Dr. Potter: You've done some work on risk factors for adverse events with silicone hydrogels. Could you tell us about that?
Dr. Szczotka-Flynn: My research has been mostly in extended wear. In both a meta-analysis and a clinical trial forum, the incidence of corneal inflammatory events with silicone hydrogel lenses was higher than that of traditional hydrogels (Szczotka-Flynn, 2007 and Invest Ophthalmol Sci, 2010).
During extended-wear, contact lens bacterial contamination is an important risk factor (Szczotka-Flynn, Invest Ophthalmol Sci, 2010). Bacterial contamination of silicone hydrogel lenses renders a patient at more than an 800% increased risk for an inflammatory event (Szczotka-Flynn, Invest Ophthalmol Sci, 2010). That's the leading risk factor, and other risk factors such as mucins in the tear film or smoking, are co-variates in the model and can modulate the response.
Dr. Sindt: I find it interesting that sometimes we move patients out of extended wear and a few months later, they experience an inflammatory event. I wonder if they reach a level of homeostasis with their cornea with extended wear, and they're introducing a bioburden to their new lenses because they're handling them more.
Dr. Szczotka-Flynn: I agree 100%. I've seen it over and over again. It's paradoxical. I agree it's probably a factor of increased bioburden due to lens handling. You need to change the solution, the lens or how they're wearing the lenses. I've often put previously successful extended wear patients back into extended wear, and in the end, they were happier with the wear schedule and they had white, quiet eyes.
THE DISCOMFORT EFFECT
Dr. Szczotka-Flynn: We found an association between lens bioburden and decreased comfort during extended wear (Szczotka-Flynn, Optom Vis Sci, 2009). I strongly believe that high bioburden decreases comfort. Perhaps it induces a subtle inflammatory state that the patient perceives as discomfort.
Dr. Brujic: I believe bacterial bioburden has an effect on comfort. If we can control the bioburden, then we can potentially decrease the severity of any subsequent biofilm. If the data show that increased bioburden decreases comfort, then we can improve comfort by controlling bioburden as much as possible by prescribing the right contact lenses and solutions.
Dr. Szczotka-Flynn: In another study (Szczotka-Flynn, Cornea, 2009) we measured the efficacy of marketed lens care solutions against the planktonic and biofilm phases of three common bacterial species (Figures 1 and 2). All of the products were effective against the planktonic or free-floating organisms. But some solutions performed significantly less well against the biofilm form. Unfortunately, the FDA doesn't require manufacturers to demonstrate efficacy against biofilm-producing clinical isolates. This is a key area of interest to me.
Dr. Potter: That information should interest any clinician because you're evaluating the organism as it is in a real-world setting as opposed to in the dish. CLS
Activity of contact lens cleaning solutions (and untreated controls) against P. aeruginosa, S. marcescens, or S. aureus grown (Figure 1) as planktonic cells, or (Figure 2) as biofilms on lotrafilcon A lenses. The effect of contact lens care solutions against planktonically grown cells was evaluated according to International Organization for Standardization (ISO 14729) Stand Alone Procedure guidelines. The effect of contact lens care solutions against mature biofilm was assessed by measuring the remaining log CFU after soaking biofilm coated lenses in each manufacturer's solution for the recommended soak time. Data represent Mean ± Standard Deviation, for at least three replicates.