An evidence-based evaluation of corneal inflammatory events in contact lens wearers.

Infiltrrative Keratitis & MPDS: Peer Reviewed

Contact Lenses and Infiltrative Keratitis

An evidence-based evaluation of corneal inflammatory events in contact lens wearers.

By Christopher W. Lievens, OD, MS, FAAO

images Dr. Lievens is the chief of staff of The Eye Center at Southern College of Optometry. He also holds the academic rank of professor. He was the chief of Aerospace Optometry at the Pentagon before joining SCO. Dr. Lievens has published scientific research and has lectured on topics dealing with eye disease, contact lens solutions, and optometric management, and he is the co-creator of the funduscopic grading card. He has received research funding from Alcon, Allergan, EyeGate, and Merck, and has received honoraria from Alcon, Transitions, Zeiss, and VSP.

The association of contact lenses and corneal infiltrates has long been recognized. Inflitrates are accumulations of inflammatory cells that cluster within corneal tissue in response to a variety of inciting stimuli (Szczotka-Flynn, 2012). The inflammatory corneal events associated with contact lens wear range from mild, self-limiting conditions of little clinical importance to severe cases associated with frank microbial keratitis that may result in permanent vision loss (Efron and Morgan, 2006).

Corneal infiltrates that resolve within a few days without treatment can initially appear very similar to infiltrates that herald far more serious infections (Chalmers et al, 2007). This makes it imperative for clinicians to be able to recognize and differentiate sterile versus infectious infiltrates. The literature, particularly the seminal article by Stein, offers guidance to appropriate differential diagnosis (Stein et al, 1988; Aasuri, 2003).

Within the past four years, a growing number of reports have suggested a link between contact lens multipurpose disinfecting care solutions (MPDSs) and an infiltrative response, more so with silicone hydrogel lens materials (Kilvington et al, 2013; Szczotka-Flynn, 2012; Stahl, 2011; Carnt, 2009). Similar reports circulating more than a decade ago associated with lens care products and traditional hydrogel lenses were never substantiated. The association of infiltrates with lenses, lens care products, or both, represents a unique risk factor that has been somewhat contentious, particularly due to the commercial implications.

However, the complex and controversial nature of lens-related infiltrates has been previously recognized (Cohen, 2000). Risk factors for corneal infiltrates typically involve at least one of these factors: high levels of bacteria associated with poor contact lens wear or lens care compliance (overwear, poor habit, failure to wash hands, etc.), overgrowth of normal or abnormal eyelid flora often associated with blepharitis or meibomian gland dysfunction (MGD), and hypoxic conditions due to overnight wear especially with lower-Dk lenses (Szczotka-Flynn, 2007). Should a link between specific lenses and/or lens care products be validated, it could prompt significant changes in the prescribing habits of many contact lens fitters.

MPDSs are complex chemical solutions required to consistently meet challenging performance standards, primarily ensuring patient safety. This requires a careful balance between antimicrobial efficacy and ocular tissue biocompatibility reflected by correspondingly low or absent signs of corneal toxicity (Choy et al, 2012). Disruption or frank damage to the ocular surface could lead to inflammation and an infiltrative response (Carnt et al, 2009). Prior reports suggested that limbal injection and/or corneal staining could precede and pose a greater risk for a subsequent corneal infiltrate (by three times and seven times, respectively), although this is not well understood (Carnt et al, 2007; Szczotka-Flynn, 2007).

Such markers would be helpful indicators for primary eyecare practitioners to be aware of while examining both symptomatic and asymptomatic patients. Factors such as lens water content, charge, hydrophobicity, surface treatment, and lens porosity in conjunction with solution concentration, charge, ionicity, and molecular weight control the sorption of the solution components by the lens, resulting in differences in the amount of MPDS components taken up into the lens material and the subsequent release onto the ocular surface (Jones and Powell, 2013).

Recent evidence has also suggested that MPDSs can alter the metabolic activity of corneal epithelial cells (Cole et al, 2012). Whether or not this alteration in metabolism can prompt an infiltrative event is an important question.

The Diagnostic Challenge

Numerous lectures and articles over the years have addressed the challenge of determining the correct diagnosis when clinicians are presented with corneal inflammatory signs. Corneal asymptomatic infiltrative events (Als), microbial keratitis (MK), contact lens-induced peripheral ulcers (CLPUs), infiltrative keratitis (IK), and contact lens-induced acute red eye (CLARE) all share commonalities that can make them difficult to distinguish from each other (Efron and Morgan, 2006; Stein et al, 1988).


Risk Factors for Sterile Infiltrates in Contact Lens Wearers*

• Omitted/Infrequent lens disinfection

• Bacterial contamination of the storage case

• Extended wear of hydrogel lenses

• Toxic corneal staining

• Limbal redness

• Younger age (0 years to 25 years)

• Older age (50+ years)

• Smoking

• High ametropia

• Lower socioeconomic class

*Stapleton et al, 2007

A retrospective review of 111 contact lens-associated events encompassing the aforementioned conditions was conducted, with considerable overlap found among the clinical presentations (Efron and Morgan, 2006). It therefore may not always be possible to clinically differentiate these conditions with any degree of certainty. This is a primary reason why many clinicians consider some infiltrative events as potentially infectious and treat them accordingly.

The challenge of making the appropriate diagnosis in similar conditions with vastly different treatments is not new by any means. In fact, a study presented at the 2010 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting found that corneal specialists were able to correctly differentiate between bacterial and fungal infections only 65.5 percent of the time (Shovlin, 2011). It can easily be argued that corneal inflammatory and infiltrative events are even more confounding.

This notion could partly explain why there is substantial disagreement with regard to the incidence of corneal findings in general. A review of all landmark studies reviewing infiltrates in contact lens wear found that most reports had a range in incidence from 0.5 percent to 3.3 percent per year for symptomatic cases (with some non-U.S. studies reporting an incidence with more widely divergent numbers than these) (Stapleton et al, 2007). Table 1 shows the combined risk factors for sterile infiltrates in contact lens wearers from all the reviewed studies (Stapleton et al, 2007).

The Real Risks for Infection

Bacterial overgrowth and transfer of microbes on the contact lens surface to the ocular surface during lens handling and application can predispose wearers to varied complications (Willcox et al, 2011). Bacterial contamination of hydrogel contact lenses during asymptomatic wear may occur at a 50-percent rate and typically involves a relatively short list of microorganisms (Willcox et al, 2011).

Contamination generally occurs as a result of poor hygiene during lens storage and handling and/or domestic water supply contamination (Willcox et al, 1997). Lens storage systems and the variety of available lens cases pose additional challenges and confounding variables compounded by the range of patient behaviors and practitioner recommendations regarding case disposal and disinfection. A 2010 investigation of lens case contamination during use with silicone hydrogel lenses and different disinfecting care solutions found an overall contamination rate of 85 percent (Willcox et al, 2010). In contrast to previously published work, cases exposed to hydrogen peroxide were as frequently colonized by bacteria and fungi as those paired with MPDSs (Willcox et al, 2010).

Contact lenses are usually colonized by gram positive ocular microbiota (Willcox et al, 2011). However, certain bacteria have been found to adhere to contact lens surfaces better compared to others, notably various strains of Pseudomonas aeruginosa. Sweeney et al (2011) found that gram negative bacterial colonization was sporadic and variable. Interestingly, the specific type of pathogen overgrowth may predispose the individual to a specific diagnosis.

A 2011 paper found that gram positive bacteria on lenses (coagulase negative Staphylococci) were three times to eight times more likely to result in CLPUs and AIs, while Staphylococcus aureus and Streptococcus pneumonia were also associated with CLPUs. Gram negative bacteria (Haemophilus influenza) on lenses were five times more likely to be associated with CLARE (Willcox et al, 2011).

Testing the Variables

The broad range of responses underscores the complexity and likely multifactorial nature of contact lens-related infiltrative events and the resulting difficulty in ascertaining specific causal factors.

Recently, a large retrospective study investigated factors associated with lens-related corneal infiltrative events (CIEs), which has become a rather contentious issue. A case-control study at five U.S. schools and colleges of optometry was conducted to assess clinical associations with CIEs, including a sub-analysis evaluating the relation between soft contact lens brand and MPDS brand (Chalmers et al, 2012).

An expert panel (four experts with experience in the process of masked case adjudication for corneal inflammatory and infectious events) that was also masked to the sponsor and lens/MPDS brands reviewed 166 patient cases of symptomatic CIEs. This study sample size was not sufficient to detect an increased risk <80 percent. More than 50 lens/care solution combinations (including silicone hydrogel lenses) were evaluated, and no specific soft contact lens or lens care product brands were associated with increased risk of CIEs (Chalmers et al, 2012).

Instead, the results found a link with patient age (younger), overnight wear, silicone hydrogel lens materials in daily wear, and a protective effect with daily disposable lens wear (Chalmers, 2012). A daily disposable protective effect was also found by Chalmers who noted a 12.5-fold lower risk of IK compared to a similar patient base wearing reusable contact lenses (Chalmers et al, 2012).

Ultimately, specific care solution brands were not universally linked to infiltrative events. It is worthy to note that the Chalmers et al retrospective study design comes with limitations and is less robust in general (as compared to a prospective investigation). Researchers have found challenges in tackling a prospective study of this nature due to the low incidence of CIEs.

Additional data on CIEs comes from Szczotka-Flynn (2012) who reports early results from the Daily Wear Corneal Infiltrate Study (DWCIE). DWCIE aimed to determine the probability of a CIE during daily soft contact lens wear and to what extent microbial contamination was a risk or determining factor. Over the 12 months of the study, 92.3 percent of subjects were CIE-free. Of the 6.6 percent who were diagnosed with an infiltrative event, coagulase negative Staphylococci (CGS) was likely to be present on the lid margins. Ultimately, DWCIE revealed a sole significant finding of CGS, which contributed to a five times increased risk for CIEs.

MPDSs Off the Hook?

Specific MPDS brands have not yet been conclusively shown to be uniquely and directly linked to the development of CIEs. Recent research has been limited and has not yet been able to reproduce what anecdotal reports had earlier hypothesized, which may have been confounded by regional effects driving the CIE cases and the market share of very popular products (Szczotka-Flynn, 2013). Patients’ lens care habits and lid flora are more likely to blame for CIEs than are specific lenses or lens care products (Brujic and Brimer, 2012).

Though the chemicals in MPDSs are complex and directly affect the lens, lens case, and the cornea, in-filtrates may not be the direct and independent consequence of MPDS usage. Ultimately, more research should be undertaken to better understand this corneal phenomenon and to settle ongoing controversies surrounding the role that MPDSs may play in infiltrative keratitis. CLS

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