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Multipurpose solution may be associated with contact lens-associated infiltrative keratitis

Practitioners discuss the incidence of the condition and its possible connection with a multipurpose disinfecting solution.

Sterile corneal infiltrates, called corneal infiltrative events by various investigators, with silicone hydrogel soft contact lenses are not rare and have a number of causes, including hypoxia, solution and preservative hypersensitivity, tight lens syndrome and marginal infiltrates.

An increase in the incidence of corneal infiltrative events (CIEs) has been noted by a large number of eye care practitioners, especially those specializing in contact lenses at referral and large-volume practices. In particular, a specific type of CIE, called contact lens-associated infiltrative keratitis (CLAIK) by a number of investigators, has been on the rise. This entity presents as sterile, small, superficial, central, granular/grainy infiltrates with a varying number of symptoms, including red, irritated eyes, mildly diminished vision and contact lens intolerance, or no symptoms at all.

We began noticing this increase in CIE cases in 2009 at our respective practices. Unaware of existing research showing a correlation between Opti-Free Replenish (Alcon) and infiltrates, we were troubled to observe an increase in infiltrate cases that shared trending characteristics consistent with CLAIK. The use of Opti-Free Replenish was eventually observed as a common variable. As we were not aware of what we were seeing in the early cases, this is not an exhaustive list of patients who could have met these conditions, nor do we imply that all sterile infiltrate cases seen during this time were related to Opti-Free Replenish, but rather we intend to bring attention to the fact that this correlation is so strong that almost all memorable cases turned out to be associated with Opti-Free Replenish and not associated with other multipurpose disinfecting solutions.

Results

In an effort to catalog what we were observing, cases were collected that met a strict set of predetermined criteria. To ensure that cases met the CLAIK definition, inclusion and exclusion rules were created. These rules included the criteria presented in Tables 1 and 2.

Thirty patients met the inclusion and exclusion rules and were evaluated further. The patient demographics are summarized in Table 3. Patients ranged in age from 15 years to 55 years, with an average age of 27 years, and were predominantly female (66%). Sixty-one percent of patients experienced symptoms bilaterally and 39% in one eye only. One case was noted in 2009 and one in 2010. Fifty percent of the cases were noted in 2011 and 43% in 2012. In addition to topical steroids and/or antibiotic treatment, patients were instructed to discontinue contact lens wear until symptoms resolved and then change lens care solutions. All symptoms resolved in a timely manner without further complication.

A typical case was a 29-year-old man who presented with a 3-week history of mild eye pain, eye redness and light sensitivity in both eyes. He had been using Opti-Free Replenish multipurpose solution and Acuvue Oasys silicone hydrogel contact lenses (Johnson & Johnson Vision Care) on a daily-wear basis. The symptoms resolved after discontinuing use of contact lenses and Opti-Free Replenish for a week. However, when the patient restarted contact lenses and Opti-Free Replenish, the symptoms and infiltrative events recurred. Examination showed bilateral discrete corneal subepithelial infiltrates. The patient was treated with Dexacidin (neomycin polymyxin B dexamethasone suspension) four times a day, and the infiltrates resolved when the patient was seen 10 days later. The patient was switched to an alternative contact lens solution, and he has been asymptomatic since then. The Figure shows the multiple infiltrates in the left eye.

Multiple, diffuse infiltrates in the central and mid-peripheral cornea with accompanying signs of redness. Image: Sher NA, Jedlicka J, Golben M

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Discussion

There are a number of risk factors for corneal inflammatory events associated with contact lens wear, including tight lenses, improper lens care, bioburden on lens and lens case, overnight and extended wear, and smoking. The association of Opti-Free Replenish with adverse corneal infiltrate events has been a trend observed in multiple practice settings since it was introduced to the market and became the most commonly used contact lens solution.

Carnt and colleagues reported the incidence of adverse events for 20 varying silicone hydrogel lens and lens solution combinations over a 3-month period. A summary of CIEs from the published data showed a high incidence of CIEs and symptomatic CIEs associated with Opti-Free Replenish compared to Clear Care (Ciba Vision), Aquify (Ciba Vision) and Opti-Free Express (Alcon).

Following the suspected association between Opti-Free Replenish and CIEs, Kilvington et al, in an investigation sponsored by Abbott Labs, examined the efficacy of several leading multipurpose solutions to kill known problematic gram-negative bacteria. These organisms were cultured from the contact lens cases of individuals who had a CLAIK episode while using Opti-Free Replenish and were then cultured in a laboratory setting. Subsequently, these cultures were exposed to various multipurpose solutions and evaluated at 6 hours and 14 days. Of the evaluated solutions, only Opti-Free Replenish failed to significantly kill the bacteria — less than 1 log reduction, compared with more than 4 for RevitaLens (Abbott Medical Optics) and Biotrue (Bausch + Lomb) for the three bacterial strains tested.

Interestingly, the gram-negative bacteria Achromobacter, Stenotrophomonas maltophilia and Delftia acidovorans were the most common agents associated with the initial Opti-Free Replenish infiltrate events. Wilcox et al indicated that Achromobacter or Delftia contaminations were rare with other leading multipurpose solutions (less than 1% and 3%, respectively) compared with Opti-Free Replenish (10% and 26%, respectively).

There is also speculation that this increase in CLAIK cases associated with Opti-Free Replenish is related to a large market share and subsequently a larger population to draw from. Kislan et al said the percentage of infiltrate keratitis events is considerably elevated when compared with market share (83.3% of cases compared with around 27% of the market share).

Wiley et al established a strong correlation between diversity of bacterial populations, specifically the predominance of Achromobacter, Stenotrophomonas maltophilia and Delftia acidovorans, in patients with infiltrative events with severity of the condition and visual acuity. One can speculate that the presence of these organisms may vary by geographic location and partially explain the variation in seeing this problem depending on location. This finding, in conjunction with those of Kilvington et al, suggests that Opti-Free Replenish has a compromised biocidal efficacy against several types of microorganisms, which raises significant concern to the clinician. Kislan et al observed this phenomenon in their 2011 investigation that demonstrated that 71% of cases were associated with Opti-Free Replenish, and 40% of these cases were classified as severe.

A less-than-optimal multipurpose solutions that does not sufficiently kill certain gram-negative bacteria should be of concern to all clinicians. These bacteria may produce a biofilm in the contact lens case and on the lenses themselves that may initiate a corneal immune reaction in certain susceptible individuals, consistent with these findings. Supporting the theory that this is an immune reaction is the rapid improvement with topical corticosteroid treatment. Our experience shows that treatment with an antibacterial and steroid combination, or probably steroid alone, along with a change in multipurpose solution resolves the condition effectively. Patients should be strongly encouraged to continue use of the new multipurpose solution because we have observed recurrence of keratitis in patients who return to using Opti-Free Replenish. One should also be concerned with the possibility of bacterial keratitis from these organisms, although an association has not been reported.

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Chalmers et al, in an Alcon-sponsored study, performed a retrospective analysis using historical controls on the development of corneal infiltrates and found a univariate correlation between Opti-Free Replenish and infiltrate cases, but when a multivariate analysis was performed, this correlation lost its significance. However, the study failed to distinguish between CLAIK and other complications, such as solution hypersensitivity and viral keratoconjunctivitis, among others. The study also had a large design flaw in which cases with undifferentiated Opti-Free products (Replenish and Express) were randomly attributed to either Replenish or Express based on market share despite the fact that existing studies show a strong association with Replenish compared to Express.

A study by Carnt et al postulated that the presence of TearGlyde and varying concentrations of non-disinfectant reagents may account for the disparity between these two similar products. Wilcox speculated that the sodium ethylenediaminetetraacetic acid (EDTA) in Opti-Free Express compared with the no EDTA in Opti-Free Replenish may contribute to improved antimicrobial efficacy with gram-negative organisms in Opti-Free Express.

Summary

A growing number of observers have noted CLAIK associated with Opti-Free Replenish multipurpose solution that is not reported with other lens care solutions. The disinfectant properties of Opti-Free Replenish against certain gram-negative bacteria are deficient. This may lead to bacterial growth in contact lens cases and contamination of the cases with a biofilm. Exposure of certain individuals to this biofilm may produce a corneal immune response consistent with CLAIK. Practitioners are encouraged to report cases of CLAIK associated with multipurpose solutions to the manufacturers and appropriate regulatory authorities.