This investigation of a national AK outbreak identified use of a single contact lens solution as the primary risk factor for infection. AMOCMP is a multipurpose solution used for disinfecting, rinsing, cleaning, and storing lenses. Our findings indicate that the strong association between AMOCMP and AK was unlikely to have resulted from intrinsic contamination. Case-patients had a wide geographic and temporal distribution, and there were no common lot numbers among AMOCMP bottles provided by case-patients. Although 3 opened bottles of AMOCMP tested positive by PCR for Acanthamoeba spp., all unopened bottles were PCR negative, and all AMOCMP bottles were negative by culture. The positive PCR results most likely represent point-of-use contamination through contact with water or dirty hands. We suspect that AMOCMP was insufficiently active against Acanthamoeba spp., resulting in increased likelihood of infection among product users. The sources of Acanthamoeba spp. could have been varied and multiple because Acanthamoeba spp. are ubiquitous in the environment. A concurrent AK case–control study conducted in the Chicago area, which investigated 55 separate cases, also found AMOCMP to be the most important risk factor (9).

AMOCMP was introduced for sale in 2003, just before the nationwide increase in cases. This product differed from AMO Complete, the multipurpose solution that preceded it, by the addition of propylene glycol (a comfort enhancer) and taurine (a buffering agent) (12). After this outbreak, laboratory investigations found that propylene glycol may cause Acanthamoeba trophozoites to encyst, thereby making them resistant to disinfection (12,13). However, propylene glycol is not unique to AMOCMP and is an ingredient of at least 1 other multipurpose solution, as well as several brands of artificial tears. Published results on the performance of multipurpose solutions, including AMOCMP, against Acanthamoeba organisms have shown varying efficacy (14–16). Assessment of anti-Acanthamoeba solution efficacy is limited by a lack of standardized testing methods (17). FDA guidance and the International Organization for Standardization standards do not include anti-Acanthamoeba spp. testing (18). However, after this outbreak, the Ophthalmic Devices Panel of the FDA Medical Devices Advisory Committee has recommended adding Acanthamoeba spp. as a challenge organism for testing of contact lens solutions (19).

Several similarities exist between this AK outbreak and the 2006 Fusarium keratitis outbreak (7). Both outbreaks of serious corneal infections occurred primarily among users of soft contact lenses. The 3–4 year duration of the AK outbreak spanned the timeframe of the Fusarium outbreak (June 2005–June 2006). In each outbreak, the primary risk factor was use of a certain multipurpose solution; Bausch and Lomb Renu with MoistureLoc (RML) was recalled in April 2006 after its use was identified as a major risk factor for Fusarium keratitis. Neither investigation found evidence of intrinsic microbial contamination of the solution; instead, insufficient antimicrobial efficacy was hypothesized to be the primary driving force behind each epidemic. In both outbreaks, the practice of topping off solution in the lens case also emerged as an important risk factor. After the Fusarium keratitis outbreak, tests simulating the reported practices of the case-patients found that topping off reduced the antimicrobial efficacy of RML (20). Together, these outbreaks raise concern about the safety of multipurpose contact lens solutions and related consumer behavior. FDA recently discussed these concerns and recommended changes to premarket testing and labeling for contact lens solutions, including more explicit warnings against topping off the solution (19).

This investigation yielded several notable negative findings. No use of contact lens solutions other than AMOCMP was identified as a risk factor, including the 1 other multipurpose solution that contained propylene glycol. Contact lens characteristics that have been hypothesized to increase the risk for AK, such as lens material and FDA lens group (21,22), were not associated with AK in this study; nor was there statistical interaction between use of AMOCMP and characteristics of soft contact lenses. Although rubbing and rinsing of lenses during the disinfection process have been shown in laboratory studies to decrease Acanthamoeba contamination of lenses (23), we did not find these practices to be protective. Although poor contact lens hygiene is widely recognized as a risk factor for AK (24–26), in this study only the topping off of old solution emerged as an important behavioral risk factor. We speculate that the association between AK and contact lens use for <5 years may reflect a wide range of poor hygiene practices among new contact lens users. Individual hygiene lapses may not be prevalent enough to emerge as important risk factors, but in aggregate, poor hygiene practices might be more common among users of new lenses.

We also found that a wide range of behaviors that can result in exposure of contact lenses to water (e.g., showering with lenses in, rinsing lenses or cases with tap water) was not associated with AK in this study. Although such practices are generally considered to be important risk factors for AK (2,24,26), a separate case–control study among contact lens users found that water exposure was not a risk factor (27).

Some researchers have suggested that municipal water treatment type may play a role in the development of AK (28). Acanthamoeba organisms are present in the water of many households (29–32). A temporal association was noted between an increase in AK cases in the Chicago area (28) and the implementation of the Environmental Protection Agency Disinfectants and Disinfection Byproducts Rule, which was aimed at decreasing potentially harmful disinfection byproducts in water (33). To comply with this rule, many municipal water supply systems have switched from using chlorine to using chloramine as a residual drinking water disinfectant. However, no change in water disinfection type was made by the Chicago Department of Water Management during the period of interest. Chicago-area water has been continuously disinfected with chlorine for >30 years (A. Stark, City of Chicago Department of Water Management, pers. comm.). A preliminary analysis (J. Verani, unpub. data) conducted during the early phase of this investigation found that only 12 (29%) of 41 case-patients for whom water treatment data were available received household water from chloraminated systems during the month before symptom onset, compared with an estimated 32% of the general US population (34,35). These findings suggested that water disinfection type was not an important risk factor in this outbreak.

This study had several limitations. First, because AK culture is a highly specific, but insensitive, diagnostic tool (36), and because preferred diagnostic methods vary by medical center, inclusion of only patients with culture-confirmed cases may have introduced regional testing bias and underestimated the scope of the outbreak. Second, the response rate among persons approached for control interviews was low; therefore, demographic differences between cases and controls may have been due to selection bias among controls. Third, recall bias may have been introduced as we asked participants to report on contact lens product use and behavior during the previous 2 years. Fourth, misclassification bias may have been introduced because at least 2 case-patients appeared to not differentiate between use of saline and cleaning or disinfecting solutions. Fifth, because >40% of case-patients and all controls were interviewed after AMOCMP was recalled in May 2007, reporting bias may have been introduced.

Despite these limitations, among users of soft contact lenses, case-patients had almost 17 times the odds of reporting any AMOCMP use compared with matched controls, validating the results of the preliminary analysis comparing AK cases to Fusarium keratitis investigation controls (8). The use of this existing Fusarium comparison data enabled rapid public health action months before the case–control study was completed. Recent associations of 2 distinct multipurpose solutions with outbreaks of rare corneal infections highlight the need for improved surveillance to promptly detect contact lens–related outbreaks and raise concerns about the effectiveness of multipurpose solutions. Continued monitoring of AK case trends to assess the impact of the AMOCMP recall and research on the anti-Acanthamoeba efficacy of AMOCMP and other solutions are under way. Our findings highlight the importance of promoting healthy habits among contact lens users, particularly discouraging the practice of topping off solutions and reinforcing safe hygienic practices among new users of contact lenses, as well as the need for standardized anti-Acanthamoeba testing of contact lens solutions.