Article Date: 1/1/2009

Optimizing the Contact Lens Experience
THE SCIENCE OF COMFORT

Optimizing the Contact Lens Experience

Biocompatible disinfection is the first key to unlocking the science of comfort and ensuring that your patients will be successful contact lens wearers.

Arthur Epstein, OD, FAAO: Science is the foundation of clinical practice. That is perhaps the single greatest truth of medicine. It's reflected in our growing interest and reliance on evidence-based medicine and similar research-focused approaches to improved care.

Contact lens care can be defined by three key elements. You can think of them as the three sides of a triangle.

Biocompatible disinfection is first. Recent research has underscored the importance of solution-lens combinations that work synergistically with each other. Some solution-lens combinations may lead to disruption of corneal barriers.

Cleaning is second. Unclean lenses may cause discomfort and an increased risk of adverse events, such as giant papillary conjunctivitis (GPC). When taken with the typical patient's known lack of contact lens care compliance, maintaining clean contact lenses becomes quite difficult. Complex lens designs and increasingly sophisticated materials have created new challenges for patients, clinicians and solution makers.

Wetting is the final side of our triangle. Recently, we've come to realize that the dryness many of our patients experience may reflect a lack of surface wetting of their lenses. The science of wettability has advanced tremendously in just a few years, as has our appreciation for the problems that can be caused by using a nonwetting lens.

With our triangle complete, we quickly realize that we've created an equation that can describe comfort — a lens and care system combination that's compatible, cleans the lens and wets the lens. With this in mind, we begin the first of three roundtable discussions that will focus on the science of comfort.

EXPLORING THE SCIENCE OF COMFORT

Why is the science of comfort so important? Uncomfortable contact lens patients don't remain patients for long. Dropout is one of the most vexing problems we face as contact lens fitters. Each year, we lose almost as many experienced wearers as we add new ones. If lens wear becomes too inconvenient or uncomfortable, patients eventually will stop wearing lenses. In addition, there's a level of clinician comfort afforded by safety. Patients have an expectation that contact lens wear is safe. However, recent experience suggests that the safety aspect of lens wear is far more complex than previously thought.

Uncomfortable contact lens patients don't remain patients for long. Dropout is one of the most vexing problems we face as contact lens fitters. Each year, we lose almost as many experienced wearers as we add new ones.

Arthur Epstein, OD, FAAO

Once we master the science of comfort, fully understand its intricacies and apply that knowledge as we see each of our patients, we can optimize their contact lens experience.

To accomplish that goal, we've assembled an exceptional panel of experts. Our panel consists of doctors who are recognized for their clinical experience as well as their speaking and writing abilities. Each of our panelists has been involved in research in the areas we'll be discussing today, so we can expect a rather unique and interesting perspective.

As a final note before we begin, and to put things in perspective, I'd suggest that the events of the past few years have provided us with invaluable insight into what keeps contact lens wearers safe, comfortable and in their lenses. We have a great deal to discuss.

The first area I want to explore is among the hottest topics today — corneal staining. Staining has been a contentious issue, perhaps the most contentious issue in contact lenses in recent memory. Some practitioners believe staining may be a prelude to more serious complications, while others feel it's a natural and unavoidable result of contact lens wear.

A multipurpose solution shouldn't cause a severe disruption in the corneal epithelium. Corneal staining can be used to assess the degree of disruption.

BIOCOMPATIBLE DISINFECTION

Dr. Epstein: Dr. Townsend, you have a great deal of experience with contact lens-related corneal staining and you were the first to publish data on staining associated with Acuvue 2* (Vistakon) and ReNu* with MoistureLoc* (Bausch & Lomb). I know you're a fanatic about corneal staining techniques, which makes you the perfect person to begin this discussion and share your insights. I'm particularly interested in your thoughts about the clinical relevance of staining and its management.

William D. Townsend, OD, FAAO: Here's how I see it. Corneal staining appears in several forms, the most subtle being micropunctate staining, which is visible only after fluorescein instillation. It appears as very small, discrete areas that absorb stain and represent focal areas where the superficial epithelial cells have been damaged. This kind of staining often is so mild that it's difficult to visualize without the use of a barrier filter. We frequently use fluorescein and a barrier filter to enhance the visibility and appearance of corneal staining.

Management really depends on the underlying etiology of the observed staining. If it's due to ocular dryness, there are a myriad of strategies that can be implemented. In the case of contact lens-related dry eye, we strive to find the right combination of lens material and solution to help minimize staining. Everyone has favorite lens materials. My personal preferences are the Proclear and Biofinity* lenses (CooperVision Inc.) and the Oasys* material (Vistakon). In our practice, we've found that Replenish® (Alcon) is an excellent choice for patients with contact lens-related dry eye, and the Tearglyde® reconditioning agent seems to enhance comfort. I've found that switching multipurpose solution (MPS) patients to the OPTI-FREE® Replenish® formulation has resulted in reduced corneal staining. Our second go-to solution is Aquify* (CIBA Vision), which also can be helpful in contact lens-related dry eye cases.

Dr. Epstein: You raise a good point. Corneal staining does occur in dry eye as the ocular surface loses its protection. As we all know, certain combinations of lenses and solutions can produce significant amounts of staining. Do you view this differently or as part of the same continuum in the contact lens-related dry eye contact lens wearer?

Dr. Townsend: I couldn't agree more. You can have staining due to dry eye or ocular surface disease, as a result of contact lens solution interactions, or a combination of the two. In the situation of solution-lens material interaction, we look for solutions that are biocompatible with specific materials. Since Dr. Andrasko is a well-recognized authority in this area, I'll defer to him on this matter.

The issue of staining and its implications has been a very hot topic in eye care. While corneal staining is rarely sight-threatening, its presence suggests that something is impairing the ability of the epithelium to adequately protect the ocular surface. One study1 suggests patients that exhibited contact lens-related staining experienced a three-fold increase in the incidence of infiltrative events. We recognize that it's not practical to eliminate staining in all of our patients, but since it represents a breach in the epithelial surface, it makes sense to reduce the incidence and severity of staining as much as possible.

Management [of corneal staining] really depends on the underlying etiology of the observed staining. … In the case of contact lens-related dry eye, we strive to find the right combination of lens material and solution to help minimize staining.

William D. Townsend, OD, FAAO


In a nutshell, MPS preservatives and other components of the formulation that come into contact with the cornea in high concentrations can cause solution-induced staining.

Gary Andrasko, OD, MS

Dr. Epstein: Dr. Andrasko, you've done extensive research on corneal staining. I've visited your research facility and even followed your methodology, which I personally can attest, is sound. There's no doubt that your research has changed the way we look at contact lenses and contact lens care products. One thing that I suspect many of our readers would like to know is what motivated you to pursue staining research. What planted the seed in the first place?

Gary Andrasko, OD, MS: It's funny you ask, because it's a question I've been waiting to answer. As far back as 1994, Begley and colleagues2 reported solution-induced corneal staining (SICS) with one lens–solution combination. Reports of staining continued sporadically over the next decade, but really accelerated once silicone hydrogel lens materials became available.

In 2005, it was apparent that the dozen or so publications all basically found that solution-induced staining was a real issue. However, these publications described staining observed with different solution/lens combinations and using different grading scales and testing procedures. I decided that a comprehensive study3 providing an "apples-to-apples" comparison of the various MPS products, using a consistent testing methodology, was needed and would be of the greatest use to clinicians.

Dr. Epstein: Dr. Jones, you did some very early work on staining. Can you share your perspective on this research?

Lyndon W. Jones, PhD, FCOptom, FAAO: During my PhD program, I was involved in studies looking at the cleaning performance of various care regimens on contact lens materials. We conducted a study in which we fitted patients with a Group II lens in one eye and a Group IV lens in the other and got them to use three care regimens that were preserved with the same biocide (PHMB), but at three varying concentrations.

What we noted was that patients exposed to the solution with the highest concentration of PHMB exhibited a significantly greater amount of corneal staining, particularly in the eye wearing the Group II material.4 Just a year later, another study suggested that corneal staining was higher with a PHMB-preserved system (used mainly with Group I lenses) than in lenses exposed to hydrogen peroxide, and that PHMB-based systems also resulted in increased levels of palpebral changes.5

These early studies focused on the impact of the preservative alone. We found that this was probably mediated by the chemistry of the lens material4 but that finding was largely ignored — even by us.

Dr. Epstein: Dr. Andrasko, why don't you go ahead and describe what causes staining? I recently presented at the June 10, 2008, FDA Contact Lens Panel Meeting and one of the key issues discussed was uptake and release. Can you explain what it is, what it means and its relevance to the average contact lens fitter?

Dr. Andrasko: Those are very important questions. In a nutshell, MPS preservatives and other components of the formulation that come in contact with the cornea in high concentrations can cause solution-induced staining.

The scenario plays out something like this. When a soft lens (traditional hydrogel or silicone hydrogel) is soaked overnight in an MPS, it acts like a sponge to absorb some components of that solution, including some preservatives. The amounts absorbed depend on several factors, including original concentration in the solution, molecular size, ionic charge and so on. When the lens is removed from the case and placed on the eye, the absorbed solution components can be released onto the ocular surface at high concentrations due to the small volume of the tear film.

Whether or not staining occurs depends on the amount released into the tear film as well as the relative toxicity of the particular solution component. Our research has shown that, in general, solutions containing a PHMB preservative tend to induce more staining when compared to those containing POLYQUAD® or a hydrogen peroxide system, particularly with certain lens materials.

Dr. Epstein: One of the other issues associated with uptake is removal of the disinfectant from the solution, where it's doing its job of disinfection. That's another area that likely will be a regulatory focus. With too much uptake, you not only create a potential for high release of disinfectant onto the ocular surface, but you also mitigate the effect of the disinfectant, which has been sequestered inside the lens material. I think we'll be hearing much more about uptake and release dynamics, kill curves and cytotoxicity as new testing protocols are debated and regulations promulgated.

Dr. Jones, you were among the first to report staining with silicone hydrogel materials and lens care products. Can you share how you discovered this and your current perspective?

Dr. Jones: When silicone hydrogels initially were introduced, they were primarily intended for use as continuous wear materials, in which patients wore them for up to 30 nights. However, despite their very high oxygen permeability and the fact that early clinical data showed they performed extremely well from a physiological stand-point,6,7 many practitioners were reluctant to prescribe lenses for overnight wear, having seen patients exhibit significant complications from overnight wear of traditional hydrogel materials. As a result, many practitioners started using silicone hydrogels for daily wear and we became interested in how these materials would perform when used in this way.

An obvious aspect to examine was their performance with various care systems, as nothing in this area was published at that time. We began conducting a number of studies investigating the way in which silicone hydrogels performed with various care regimens.

In our first clinical study, which was subsequently published in Optometry and Vision Science,7 we were primarily evaluating the comfort and clinical performance of two of the most popular preserved one-bottle care systems (ReNu MultiPlus* [Bausch & Lomb] and OPTI-FREE® EXPRESS® [Alcon]), when used with one of the two silicone hydrogel materials available at that time (PureVision* [Bausch & Lomb]).

The results were surprising. When used with ReNu MultiPlus*, PureVision* lenses created unacceptably high levels of corneal staining in 37% of subjects, as opposed to only 2% who used PureVision* with OPTI-FREE® EXPRESS® MPDS. Other factors, such as subjective comfort and redness, didn't differ between the two products. Furthermore, when we looked back at what care regimens the patients were using prior to entering the study, several were using ReNu* MultiPlus with conventional hydrogel materials and had no staining issues at all. We quickly realized we'd discovered a specific interaction occurring between the lens material and the solution/care regimen.

We began to realize that silicone hydrogels behave differently than conventional hydrogels when used with certain care regimens, … [suggesting] that biocompatibility issues may arise with certain combinations of silicone hydrogel products and modern care regimens.

Lyndon W. Jones, PhD, FCOptom, FAAO

Dr. Epstein: That's really remarkable. Please continue.

Dr. Jones: This was the first time we began to realize that silicone hydrogels behave differently than conventional hydrogels when used with certain care regimens. These data were the first to suggest that biocompatibility issues may arise with certain combinations of silicone hydrogel products and modern care regimens. This study was published with work by others, such as Dr. Epstein,8 who noted similar findings. Then came studies, which revealed that very little staining occurred with silicone hydrogels cleaned with hydrogen peroxide systems.9,10

Renee Garofalo of Alcon was the first to demonstrate that the staining observed had a kinetic element to it. She showed that maximum staining was observed 2 to 4 hours after lenses were inserted.10 Work by Chris Amos at CIBA Vision* demonstrated that staining wasn't merely a function of preservative concentration, as staining with products preserved at an identical concentration of PHMB was less than that observed with the ReNu* MultiPlus product.11

As a result of studies such as these, clinicians began to realize that the issue of staining with various solution-lens combinations is highly complicated, involving complex interactions between the lens, the care regimen, the patient and his typical wear time. The best method of studying these interactions was to adopt a systematic approach, which culminated in the work that resulted in the Andrasko grid and the IER matrix.12-15

Dr. Epstein: I, too, was quite surprised when I found such intense staining. We were early adopters of silicone hydrogel lenses and were stunned when we first encountered such intense staining. It really wasn't obvious at first, because a fair number of our patients wore the lenses overnight and avoided solution use. My first thought was that it was a bizarre incompatibility between the PureVision* lens and ReNu* MultiPlus contact lens solution. Interestingly, it turned out to be a much broader problem.

Dr. Schachet, you and Dr. Lebow did some pioneering work on corneal staining with several lens materials. What were your thoughts and what motivated you to investigate staining?

John L. Schachet, OD: Dr. Epstein, you and Dr. Jones were involved in what were the earliest studies addressing corneal staining with silicone hydrogels and biguanide solutions, specifically PHMB. Dr. Lebow and I felt we needed to look at traditional hydrogels, specifically differences between the interactions of PHMB and POLYQUAD® with the Acuvue 2* and Soflens66* (Bausch & Lomb) lenses.

We performed a classic, double-masked, crossover study16 to determine if there was a valid concern regarding corneal staining when using different contact lens solutions and conventional hydrogel lenses, which were by far the dominant lens type just a few years ago.

This was probably the third such study of this type. What we found was equally significant in that we observed more corneal staining with the PHMB product (ReNu* MultiPlus*) than we did with POLYQUAD® (OPTI-FREE® EXPRESS®) in any direct comparison.16

A couple of years later, we decided to look at the new biguanide solution (ReNu* with MoistureLoc*) and compare the resulting corneal staining to that of POLYQUAD® (OPTI-FREE® EXPRESS®), using the most popular silicone hydrogel on the market at that time, Acuvue Advance*. Again, we found that the biguanide product produced a greater amount of staining than did the product preserved with POLYQUAD®.17

Incidentally, as we were about to have this study published, ReNu* with MoistureLoc* was pulled from the market due to the Fusarium keratitis outbreak, so we decided not to pursue publishing it, but we did present our findings as a poster during the 2006 annual meeting of the Association for Research and Vision in Ophthalmology (ARVO).18

Dr. Epstein: Very interesting. You confirmed our findings with silicone hydrogel lenses and had similar results with conventional hydrogels. It's interesting that a scientific approach can be far more revealing than a typical clinical approach. I suspect many of our colleagues either don't look for staining or don't look for it at the right times, which is why it remained a nontopic for so long. In retrospect, I'm sure I missed a good deal of staining simply because I was looking at the wrong times — and I stain every patient religiously.

It's almost funny that despite all of this solid research and the awareness of staining, it took Dr. Andrasko's work to mainstream the issue. With that, let's have him describe the staining grid and why he decided to go with a grid format for his data.

Dr. Andrasko: Our study systematically evaluates SICS with various solutions and lens combinations. As we started collecting data, it quickly became apparent that a unique presentation format was needed to organize the enormous amount of information. I looked at my spreadsheet data and realized that an effective format would be a table or grid, identifying the solutions across the top, the lens materials down the first column and the amount of staining (% staining area) in the body of the table, at the intersection of the lens and solution being tested. This was the origin of the current staining grid.

I want my patients to use a product that has established a long-term safety profile, and products containing the POLYQUAD® preservative have proven themselves over 20 years of use. So this is good enough for me.

John L. Schachet, OD

We also added a three-color coding system to demarcate minimal, moderate and excessive amounts of staining to simplify data presentation and pattern recognition. You can find the most up-to-date results of the staining grid study online.13

Dr. Epstein: Dr. Andrasko, your research also has assessed comfort. Have you found an association with corneal staining?

Dr. Andrasko: In the Staining Grid studies, we evaluated staining type and area for each solution/lens combination tested. In addition, at each visit, patients were asked to rate their lens-wearing comfort using a 100-point visual analog scale. Our analysis of these comfort ratings is quite interesting. Solution/lens combinations inducing little or no staining are typically quite comfortable.

However, as would be expected, moderate to high amounts of SICS statistically reduce comfort as much as 24 points on the 100-point scale. Our recent article in Contact Lens Spectrum titled, "Solution-Induced Staining and Comfort During Lens Wear" presents this information in detail.19 By prescribing a biocompatible lens care product for each lens brand, the eyecare practitioner can help to maximize the patient's comfort.

Dr. Epstein: That's very interesting and your results make sense, but let me throw a curve ball. In my original study, patients had very significant staining — about 70% or so. You also reported this type of staining with the PureVision* – ReNu* MultiPlus combination. Interestingly, in my small sample, not one of the patients complained of any discomfort.8 In fact, in Dr. Jones' study, they used the word "asymptomatic" in the title of the paper.7 Garofalo also reported significant symptoms weren't correlated with extent of staining.10

I don't want to sidetrack the discussion, but I wonder if comfort and pain-like symptoms, such as photophobia or intense discomfort, are actually physiologically different. There are many confounding factors. Lenses can serve as a bandage, reducing or masking discomfort. In the study I did with Dr. Jones, the severe staining actually may have been masked by a hypoesthetic effect of the disinfectant. I published data from a small pilot study that explored that possibility several years ago,8 but your results make good sense and are consistent with what I think most of us see — patients with staining tend to be less comfortable overall.

I think if we take a step back, what we're really talking about is biocompatibility. Dr. Schachet, what clinical relevance does all of this work on biocompatibility have on patient satisfaction and your own comfort level?

Dr. Schachet: I guess that is the key question. The clinical relevance of this was what Dr. Lebow and I were questioning at the time of our research, after our results were known.

We weren't questioning what the immediate concern might be, but what the long-term concern would be with significant amounts of corneal staining over time. We all have to determine our own comfort level with corneal staining. But our anxiety was that we, as practitioners, were taking a rather cavalier approach to this issue clinically. So we questioned the long-term relevance.

Unfortunately, we still don't have all of the answers, but with recent events over the past 2 years, we clearly need to pay attention to the epithelial barrier.

The traditional disinfection capabilities of multipurpose contact lens solutions are measured against standard inoculums of common bacteria, yeast and fungi using either stand-alone or regimen testing efficacy.

Kenneth A. Lebow, OD, FAAO

Dr. Epstein: I agree with you, Dr. Schachet. Typically with infectious keratitis, we know the organism can't breach an intact epithelium, so something had to be causing sufficient trauma to allow penetration. Solution-induced corneal staining has been characterized as chemical trauma. Staining also happens to be disproportionately associated with certain solution/lens care combinations.13 That said, we'll have to wait for additional research to know if there's a staining-infection link. In the meantime, it's prudent for our colleagues to err on the side of caution by prescribing solution-lens combinations that minimize staining. Dr. Andrasko's staining grid provides a guide.

Dr. Schachet, I alluded to disinfectant uptake and release and possible loss of efficacy a bit earlier. Modern lens care products are very complex. So how important is disinfection efficacy? Please take a moment and share your thoughts from the perspective of patient care and also address any differences between products.

Dr. Schachet: At one time, we tended to minimize this issue. How many patients would walk in who used saline with no disinfectant or cleaner? Few, if any, ever seemed to have problems. Today, after the Fusarium keratitis and Acanthamoeba keratitis outbreaks, we've really had to rethink the situation.

Clearly, there was a difference in disinfection efficacy, certainly of the recalled products. But patients and doctors don't give it much thought. The bottom line is simple — PHMB is a good disinfectant. Hydrogen peroxide is a good disinfection agent and POLYQUAD®/ALDOX® are good disinfection agents. So, why is there reason for concern?

First, we found several solutions containing PHMB to be a contributor to corneal staining when used with some traditional and silicone hydrogel lenses, so that's a concern. Second, hydrogen peroxide disinfects well, but once the peroxide is neutralized, the contact lenses are sitting in saline and organisms actually can regrow.20 So that's a concern as well.

Products preserved with POLYQUAD® (polyquaternium-1) and ALDOX® (myristamidopropyl dimethylamine) not only disinfect well, but continue to provide effective disinfection over a 30-day period of continuous lens storage. This is an issue for our patients and a comfort level issue for us as their doctors. I want my patients to use a product that has established a long-term safety profile, and products containing the POLYQUAD® preservative have proven themselves over 20 years of use. So this is good enough for me.

Dr. Epstein: I also think there's even more to the equation. Antibiotics are specific killers. They typically target one or two aspects of cell function and can be tailored for greatest effect on specific organism groups. On the other hand, disinfectants are more indiscriminate in their killing ability, yet they can have significant efficacy limitations with certain organisms. With antibiotics, we often combine them for synergy where the effect of two is greater than the sum. How do you see that playing out in contact lens disinfection?

Kenneth A. Lebow, OD, FAAO: The traditional disinfection capabilities of multipurpose contact lens solutions are measured against standard inoculums of common bacteria, yeast and fungi using either stand-alone or regimen testing efficacy. Recently, despite passing mandated testing criteria, two multipurpose care systems failed in the marketplace (one with PHMB and the other with Alexidine* [Renu, Bausch & Lomb]) resulting in significant Fusarium keratitis and Acanthamoeba keratitis human ocular infections. The preservative in each of these recalled solutions was a biguanide family disinfectant.

Alcon's OPTI-FREE® RepleniSH® MPDS, unlike biguanide-based systems, wasn't associated with increased rates of ocular infection and has never been involved in a product recall.

I believe one of the reasons is that OPTI-FREE® RepleniSH® uses a uniquely different dual disinfectant system – POLYQUAD® and ALDOX® . It has a distinct advantage in disinfection because the dual disinfecting system provides good coverage against bacteria and fungi,21,22 very much like the combination antibiotics you mentioned, Dr. Epstein. Moreover, ALDOX® antimicrobial provides activity against fungi and both the cyst and troph forms of Acanthamoeba by penetrating the protective outer coating of fungal cells and Acanthamoeba cysts disrupting the cell wall resulting in cell death.23

The dual disinfection system in OPTI-FREE, which uses POLYQUAD® and ALDOX®, provides good coverage against bacteria and fungi.

Compared to Alexidine* and polyhexamethylene biguanide preservatives, POLYQUAD® is a significantly larger molecular weight cationic (positively charged) disinfectant. According to Jerry Paugh's research, it maintains corneal barrier function by minimizing corneal damage (staining) and by maintaining normal corneal permeability.24

Dr. Epstein: Thanks, Dr. Lebow. I believe many of the next-generation lens care products should include dual disinfectant systems. I see that as the way of the future, given what should be strong resolve to avoid another product recall.

Now a question for you, Dr. Townsend. There's been a good deal of discussion regarding uptake and release of disinfectants from the lens. Uptake is thought to remove disinfectant from the solution in the case, rendering the solution less effective, and release appears to increase levels of disinfectant in the precorneal tear film to potentially toxic levels. This is thought to be the cause of contact lens-related corneal staining. How do you see this issue?

Dr. Townsend: We know that preservatives are absorbed or adsorbed by lenses. I believe that if a preservative is concentrated in the lens matrix, it may be less effective at disinfecting the surface. Also, we know from Dr. Garofalo's work that the release of preservatives can cause variable amounts of staining in the first few hours after lens insertion with certain lenses — particularly in specific biguanide solutions.3

Uptake and release vary depending upon the solution formulation and the lens material. High rates of uptake can reduce disinfection efficacy, while high rates of release can produce toxic concentrations of a solution component in the precorneal tear film and lead to surface compromise. This can be seen clinically as staining. Interestingly, this phenomenon can be relatively asymptomatic.

For that reason, it's important to understand the uptake and release relationships for different lenses and solutions.

Dr. Epstein: I agree. This is something I suspect regulatory agencies will be looking into as they develop new standards.

As you can see, biocompatible disinfection is a hot topic in optometry and a very important aspect of contact lens care today. There are many opinions regarding this topic. We hope this discussion has helped you better understand the issues we face as practitioners. I hope you enjoyed this first installment in a three-part series. Please look for future installments in the months ahead. CLS

*Trademarks are the property of their respective owners

REFERENCES
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  14. Carnt N, Willcox M, Evans V, et al. Corneal staining: The IER matrix study. Contact Lens Spectrum 2007:38-43.
  15. Carnt N, Evans V, Holden B, et al. IER matrix update: adding another silicone hydrogel. Contact Lens Spectrum 2008:28-35.
  16. Lebow KA, Schachet JL. Evaluation of corneal staining and patient preference with use of three multi-purpose solutions and two brands of soft contact lenses. Eye and Contact Lens 2003;29:213-220.
  17. Lebow K and Schachet JL. Differences in clinical performance of multipurpose solutions with a silicone hydrogel lens. Invest Ophthalmol Vis Sci 2006:47:E-Abstract 99.
  18. Schachet JL, Lebow KA. Corneal and conjunctival staining with the new bigranide, alexidine preserved solution. Poster presented during the annual meeting of the Association for Research in Vision and Ophthalmology, May 2006.
  19. Andrasko G. Solution-induced staining and comfort during lens wear. Contact Lens Spectrum; September 2008:33-35.
  20. Rosenthal R, McNaniee L, Schlech B. Continuous antimicrobial activity of contact lens disinfectants. Contact Lens Forum 1988;11;72-75.
  21. Codling CE, Maillard J, Russell AD. Aspects of the antimicrobial mechanisms of action of a polyquaternium and amidoamide. J Antimicrob Chemother 2003;51:1152-1158.
  22. Rosenthal RA, McAnally CL, McNamee LS, Buck SL, Schlitzer RL, Stone RP. Broad spectrum antimicrobial activity of a new multi-purpose disinfecting solution. CLAO 2000;26:120-126.
  23. Rosenthal RA, Bell WM, Henry CL, Schlech BA. Antimicrobial spectrum of a new contact lens disinfectant. AAOptom, San Diego, CA. Abstract & Poster: 99 page 66. December 2005.
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Contact Lens Spectrum, Issue: January 2009