Article Date: 3/1/2009

Understanding and Managing Risk in Contact Lens Wear
CONTINUING EDUCATION

Understanding and Managing Risk in Contact Lens Wear

By Arthur Epstein, OD, FAAO

The risks associated with contact lens wear have long remained more of a public fear than a professional concern. The lack of professional concern may seem odd, but the reasons for it are relatively straightforward. Most contact lens fitters view contact lenses as refractive options rather than medical devices. We can trace the origins of this perspective to the introduction of easily fitted and comfortable soft lenses in 1971. This perspective was reinforced with the introduction of commoditized disposable lenses in 1987.

Unlike spectacles, which have little risk, but similar to most other medical devices, contact lenses possess elements of risk and benefit. This article explores newer concepts regarding the risks associated with contact lens wear and lens care, their origins and how we as clinicians can better recognize and understand these risks and develop strategies to minimize them. I will examine scientific research and offer clinical perspectives to help guide the care of your patients.

DEFINING RISK

Risk is defined by two key parameters: harm and uncertainty. Essentially, measures of risk represent the uncertainty of whether or not harm will occur under given circumstances. Harm can vary tremendously in extent and therefore must be viewed as relative. Minor harm, such as temporary contact lens irritation, can be considered of little concern. Of note, because of their minimal impact, the significance of most minor signs or symptoms may remain unclear to the patient; however, they can provide important clues for the clinician.

Harm leading to permanent injury, such as sight-threatening infection, is of enormous concern to both patient and clinician. Although the potential for harm to an individual contact lens patient is neither well understood nor easily calculable for most complications, recent events have revealed and clarified potential causes of serious contact lens complications, such as microbial keratitis.

Risk is nothing new to contact lens wear. Although relatively rare, adverse event reports associated with soft lenses, including serious infections, were reported as far back as the early 1970s — just a few years after the introduction of the first soft lenses. Sporadic reports of adverse events continued, peaking with the 1989 New England Journal of Medicine report, which linked overnight wear with microbial keratitis.1

Even with the growing interest in contact lens complications that drove an optometric expansion into therapeutic eye care, and despite what might best be described as warning signs, many contact lens fitters continued, and perhaps continue, to view contact lenses as fundamentally nonmedical in nature. Recent events have shown this approach is perilous.

LEARNING FROM FAILURE

While patient noncompliance has remained a concern since the introduction of soft contact lenses, salt tablet-based saline and heat disinfection lens care systems have evolved to provide effective disinfection, acceptable lens cleaning and, for newer products, improved patient comfort. Or so it seemed.

In July 2005, reports of unusually high rates of infection among soft lens wearers surfaced in Hong Kong. By early 2006, Singapore linked a surge in cases of Fusarium keratitis to Bausch & Lomb solutions. In March 2006, David Chu, MD, reported three cases of Fusarium keratitis in his Northern New Jersey ophthalmology practice to Bausch & Lomb and then to the CDC.2

The CDC investigation linked ReNu with MoistureLoc (Bausch & Lomb) to the outbreak. After extensive investigation and numerous reports of infection, ReNu with MoistureLoc was recalled from the global market in May 2006 and the outbreak faded.3

Approximately 1 year later, in May 2007, Charlotte Joslin, OD, and her team from the University of Illinois and the Illinois Dept of Public Health notified the CDC of a possible outbreak of Acanthamoeba in the Chicago area. After preliminary surveys were completed, a multistate investigation was launched. A strong association of Acanthamoeba cases with the use of Complete MoisturePlus (Advanced Medical Optics) was found and reported to the FDA on May 24, 2007. The data was shared with state and local health departments the following day, and Complete MoisturePlus was recalled globally May 26.4

The CDC investigation compared Acanthamoeba case patients to controls from the 2006 Fusarium outbreak and generated data and conclusions applicable to both of the outbreaks, yet broad enough to be of overall clinical value.5

Of the myriad factors investigated by the CDC in both outbreaks, a surprising number were found to be noncontributory, including many of the "usual suspects."5

In both outbreaks, the solutions themselves were the primary risk for infection.3,5 For example, patients diagnosed with Acanthamoeba keratitis were 17 times more likely to have used Complete MoisturePlus than any other lens care product.5 Joslin and colleagues reported similar findings.6

Complete MoisturePlus had been on the U.S. market since August 2003 — nearly 4 years before the formulation was linked to sight-threatening Acanthamoeba infection. ReNu with MoistureLoc was on the market for approximately 15 months before problems with the formulation were suspected. These delays in detection underscore the product testing and epidemiologic challenges inherent in identifying and investigating what are typically low-incidence contact lens complications. It also makes these two outbreaks of tremendous value for better understanding the genesis of infection in lens wearers.

Some questioned if the high frequency associated with specific solutions masked involvement of other products. In analyzing data from the Fusarium outbreak, the CDC found a statistical link only with ReNu with MoistureLoc; however, Saw7 and colleagues reported a statistical link between Fusarium keratitis and ReNu MultiPlus as well. No other links were identified.

Perhaps the most intriguing data to derive from both outbreaks were the lack of correlation between infections and lens type, wearing regimens and patient hygiene practices. In analyzing data from the Acanthamoeba outbreak, the CDC reported no correlation between infection and the following factors5:

■ Contact lens characteristics
– FDA group, silicone hydrogel, surface treated

■ Contact lens wearing habits
– Daily vs. extended wear
– Hours/day and days/week
– Overnight wear

■ Hygiene and disinfection
– Rubbing or rinsing lenses during disinfection
– Washing hands before cleaning lenses
– Handling lenses with wet hands
– Hours storing lenses in case

■ Water exposure while wearing lenses
– Showering, bathing, swimming in pool

Similar findings were reported during the Fusarium outbreak.3 With the exception of topping off old solution in the lens case and additional risk for patients with less than 5 years of lens wear experience, no other factors were found to be linked to infection.

The association with topping off old solution is easily explained by the progressive loss of disinfectant efficacy over time seen with certain lens-solution combinations due to preservative uptake. Topping off adds little disinfectant to the already disinfectant-depleted, nearly filled case. This critical issue will be explored in considerable detail.

Poor hygiene has long been believed to be associated with contact lens-related complications, particularly infection, yet lax hygiene practices were not shown to play a role in these recently investigated episodes of contact lens infection.

RISK FACTORS FOR INFECTION

Among the many lessons learned from the Fusarium and Acanthamoeba outbreaks, we can surmise that current FDA testing protocols are inadequate to ensure that all approved lens care products remain safe under typical conditions of use.

While new testing procedures are being proposed and reviewed, it's essential that clinicians understand the risk factors involved with contact lens care systems and act to reduce risk until new testing protocols are developed and validated. Put simply, understanding risk factors can assist in preventing risk from becoming an unpleasant clinical reality.

Microbial keratitis occurs only when the following conditions occur:

1. Pathogens must be present in the ocular environment

2. Pathogens must be at infectious levels

3. Ocular barriers and defenses to infection are overcome.

All products approved for use in the United States, including ReNu with MoistureLoc and Complete MoisturePlus, met relatively robust and stringent FDA/ISO disinfection standards. So, how could these FDA-approved products have been associated with such high rates of infection?

For pathogens to have survived and caused infection, disinfection must have been ineffective. ReNu with MoistureLoc failed to kill strains of Fusarium and possibly other organisms, while Complete MoisturePlus was ineffective against Acanthamoeba.4,6,8 If either product had been effective, relatively large-scale outbreaks wouldn't have occurred. Clearly, something within the use or performance patterns of these products reduced disinfectant efficacy against the causative pathogens.

Among the first to describe solution-lens interactions, Dannelley9 reported uptake of polyhexamethylene biguanide (PHMB) into Acuvue (Vistakon) lenses resulting in disinfection failure. Solution effectiveness requires disinfectant levels to remain at lethal levels throughout the disinfection/storage cycle. Uptake of disinfectant into the case or the lens reduces levels within the solution and can cause subsequent disinfection failure. This appears to have been a key factor in the failure of ReNu with MoistureLoc.10

The source of Complete MoisturePlus failure appears to be more complex.5,11 In addition to disinfectant inefficacy, intrinsic factors, such as the presence of taurine, polypropylene glycol and possibly other constituents in the MoisturePlus formulation, may have enhanced encystment and therefore facilitated survival of Acanthamoeba organisms.12 Of note, both solution failures involved biguanide-based disinfectants, which previously have been shown to adsorb into the lens.9,10

There's evidence that the design of the two recalled solutions contributed to the high infection rate either by protecting the pathogens or by facilitating their growth.2,12,13 Both solutions contained cellulose-based polymers, designed to enhance and prolong lens surface wetting. The addition of possibly nutritive lens care components may have had unintended consequences.2

Differential infection rates depicted in Table 1 show clear distinctions between products with polyquad and hydrogen peroxide-based products, indicating negligible rates of infection.

GENESIS OF INFECTION — MINIMIZING RISK

Few topics within the contact lens community have generated as much debate as have discussions regarding the relevance of corneal staining and its possible role in microbial keratitis. While staining occurs spontaneously and transiently in a majority of patients, significant and possibly relevant staining has been associated with contact lens wear.14 Until recently, most clinicians considered staining a visible sign that a breach in the outer epithelial barriers, through which fluorescein penetrated, had occurred.

Disruption to the corneal epithelium has long been considered a risk factor for infection.15 Most reports regarding contact lens-related staining associate it with PHMB-based care products.16-19 Research by Paugh and associates20 demonstrated the effectiveness of carboxymethylcellulose in sequestering PHMB thus reducing staining levels due to PHMB toxicity — indirectly confirming the role of PHMB in staining.

Garofalo and colleagues21 showed that staining is time dependent. Subsequent work by Andrasko and Ryen22 demonstrated differential staining levels associated with solution-lens material combinations (Figure 1). The Andrasko grid (Table 2) is considered by many to be of tremendous utility for predicting compatibility between various lens and solution combinations.22

Figure 1. Corneal staining examples: Sodium fluorescein is used to demonstrate the degree of staining that can occur with different lens-solution combinations. Minimal corneal staining is visible with a Polyquad solution (left), but excessive staining is apparent with a PHMB-based Biguanide solution (right).

Because most pathogens can't penetrate intact epithelium, prior trauma is required to create a portal for entry.15 This is especially true for fungi, such as Fusarium, which is effectively blocked by normal intact ocular surface epithelium and where infection is almost always associated with trauma.23,24 Corneal trauma also may play a role in Acanthamoeba keratitis.25

As discussed previously, uptake of disinfectant can lower disinfectant levels to sublethal and render a solution ineffective. Likewise, release of disinfectant upon placement of a lens on the surface of the eye may produce precorneal tear film levels that are sufficiently high as to be epitheliotoxic.17,26

Given the likely role of surface disruption in infection, until definitively proven otherwise, corneal staining must remain suspect as a risk factor for contact lens-related microbial keratitis. While firm evidence for microbial keratitis doesn't yet exist, primarily due to the scarcity of microbial keratitis cases, prior corneal staining has been linked to infiltrative keratitis.27 While some would argue that some staining isn't a "bad thing," certainly less staining is always preferable to more staining. The Andrasko grid can be of significant assistance in predicting high-staining solution-lens combinations and avoiding them.

OTHER STRATEGIES FOR REDUCING RISK

Both outbreaks were followed by a good deal of introspection and discussion about strategies for reducing the risk of microbial keratitis in contact lens wearers. Improved disinfection standards being discussed will no doubt help. In the interim, prescribing biocompatible lens-solution combinations is a simple and logical approach to avoiding problems. However, because microbial keratitis is likely multifactorial, it's important to consider other strategies that might reduce the risk for our contact lens patients.

Improving compliance is certainly at the top of the wish list for most medical practitioners. Compliance is a major issue that affects health care universally, and contact lens wearers seem to be an especially noncomplaint group.28 No-rub solutions were introduced to make lens care more convenient, but their enhanced disinfection efficacy also has served to create a safety net for less-than-compliant patients.

I presented data at the recent FDA Lens Care Panel meeting that reported rubbing behavior was unchanged by the introduction of no-rub solutions or even by the intense publicity surrounding the Fusarium outbreak. While some have pronounced rubbing an effective strategy for reducing microbial keratitis,29 neither lens rubbing nor even hand-washing had a protective effect during either outbreak.3,5 Rubbing may be useful for patients who experience heavy protein or lipid depositing, but it appears to be of little benefit in reducing the risk of contact lens-related microbial keratitis. Solution disinfectant efficacy appears to be a far more important factor in minimizing risk.

Other risk reduction strategies include the use of peroxide disinfection, silicone hydrogel materials or single-use lenses; however, there is evidence to suggest these alternatives may not provide increased protection.

Despite being somewhat more complicated to use, peroxide disinfection may be beneficial in patients who have demonstrated sensitivity to multipurpose disinfecting solution (MPDS) preservatives; however, current peroxide products offer little or no advantage over MPDS products from a disinfection efficacy perspective. Reports have been contradictory with some showing limited anti-acanthamoebal effectiveness for peroxide-based products; especially single-step systems. Other studies have shown superiority for MPDS systems.30,31

Likewise, neither silicone hydrogel nor single-use, daily disposable lenses have reduced the incidence of contact lensrelated microbial keratitis.32,33 This suggests that existing contact lens technology has reached its limits relative to reducing risk. Further reduction in contact lens-related risk may be impossible, pending the introduction of more advanced, technology-driven lens care disinfection systems or effective antimicrobial cases and lens surfaces.

MINIMIZE RISKS, MAXIMIZE BENEFITS FOR YOUR PATIENTS

As with all medical devices, contact lenses possess risk and benefit. Outbreaks of microbial keratitis associated with specific lens care products provide insight into the genesis of infection and how risk can be managed. The lessons learned reveal that the perfect contact lens or lens care system does not exist. Despite this, clinical experience has proven contact lenses to be of far greater benefit than risk for most patients.

Understanding risk — and taking concrete steps to minimize it — is a good start. Treating contact lenses like medical devices, then prescribing lenses and care products that are most appropriate for each individual patient is the best approach to maximizing benefit and minimizing risk. CLS

Dr. Epstein is a senior partner in North Shore Contact Lens and Vision Consultants of Rosyln Heights, New York. He's on the attending staff of North Shore University Hospital, NYU School of Medicine, and is a clinical adjunct assistant professor of Northeastern State University College of Optometry, Tahlequah, Okla. Dr. Epstein has served as a consultant or advisor to numerouscompanies, including Alcon, Advanced Vision Research and Vistakon. He has received research funding from Alcon.

REFERENCES
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Contact Lens Spectrum, Issue: March 2009