In aggregate, previously reported data have suggested that infectious keratitis in contact lens wearers occurs because microbes gain access to the contact lens paraphernalia, particularly the case during conditions of use and misuse of lenses. There the microbes can reproduce, attach to contact lenses stored in the case, and subsequently be transferred to the eye. In most cases, no clinically apparent infection ensues. In some cases, perhaps when host defenses are reduced because of systemic immunosuppression, local tear deficiency, or trauma to the epithelium, infectious keratitis develops.
8,14,17,19,21
Species of
Fusarium and
Acanthamoeba, although common in the environment, are rarely the cause of contact lens–associated microbial keratitis.
8,17 –21 The rare involvement of these microorganisms may be attributed to their low virulence, common host-resistance factors,
8,14,16 –18 and possibly the susceptibility of most conidia, trophozoites, and precysts at low densities to most MPSs. We suggest, however, that the capacity of some strains to form dormant stages rapidly in drying MPSs increases their chances of survival in or on the contact lens case and the risk of potential involvement in disease. Our clinical isolates of
Fusarium from the 2004–2006 keratitis outbreak have been observed to survive and amplify in partially dried MPSs after approximately 24 hours but not in nonevaporated MPSs.
11,12,17 Levy et al.
10 reported decreased efficacy of evaporated RML for a clinical isolate of
Fusarium. Hume et al.
45 reported that 2 of 10 clinical isolates of
Fusarium were not susceptible to disinfection with current MPSs. About half of their 10 clinical isolates (with a modified inocula procedure that included hyphal elements with the conidia) did not meet the one log ISO standard disinfection criteria for most MPSs studied.
45
Our previous observations of ex vivo lenses indicated that the involvement of chlamydoconidia formation during conditions of actual use of MPSs cannot be excluded.
11,17 Fusaria associated with the US 2004–2006 outbreak from varied geographical and clinical sources can attach to and penetrate hydrogel lenses and produce chlamydoconidia.
12,17,46 We speculated that wearing of lenses penetrated by fusaria increased the risk of infection, but supportive data were sparse.
17 Ultimately, the association of fusaria with worn contact lens may be most affected by personal hygiene practices and host-tear interactions.
47
Our current data and the literature
19,21,48 suggest that evaporation and drying of various MPSs induce
Acanthamoeba trophozoites to form some dormant and mature (double-walled) cysts within 24 hours. Sriram et al.
34 reported that mature or aged
Acanthamoeba cysts in dried agar, including cysts formed by isolates from keratitis patients, remained viable after 20 years. As few as 100 mature cysts of
Acanthamoeba have been shown to yield survivors after 6- and 24-hour exposures to the same MPSs we studied herein.
48 Mature or double-walled cysts of wild-type
Acanthamoeba are presumed highly resistant to adverse environmental conditions. We speculate that components of drying MPSs (e.g., propylene glycol derivatives complexed with hemicelluloses in CMP) may harbor cysts and precysts of
Acanthamoeba (and, in the case of the RML formulation the conidia or chlamydoconidia of fusaria) for extended periods in or on contact lens cases. Our data suggest that both rapid (within 24 hours) and delayed (∼168 hours) induction and differentiation of trophozoites to mature cysts may occur within these drying residues. Possibly, excessive repeated rinsing with certain MPSs and air-drying of cases as currently recommended could, unexpectedly, build up residues that harbor dormant stages and increase the risk of contamination with microorganisms with lifecycle properties similar to those of
Fusarium and
Acanthamoeba. The irregular but common practice of “ topping-off” (reuse of solution, a common practice identified among patients of both outbreaks) may also associate with the development of dried residues in and on the case.
Several investigations
28,44 have reported that
Acanthamoeba trophozoites form only immature cysts after short-term exposures to various MPSs, particularly those containing PHMB. We observed, however, the formation of mature cysts, often in aggregates, in 24-hour dried residues of MPSs, particularly CMP. This suggests that these areas of the “dried films” lacked or were deficient for their anti-amoeba properties. The water content of the films was in equilibrium with the ambient atmospheric conditions and hydroscopic components or regions of the “dried films” retained or adsorbed water throughout the study period. Certain “dried” residues retained or developed liquid globules with the rare presence of internal trophozoites. The extent to which our test conditions mimic in-use conditions for contact lens care with MPSs is unknown.
Although undocumented, a decline in contact lens-associated AK in the United States was suggested in the early 2000s before the availability of CMP.
43,44,49 The increasing reports of AK in 2006–2007 in the United States occurred in conjunction with decreased AIDS-associated infectious keratitis, increased “no-rub” MPS use, the increased popularity of silicone hydrogel lenses, enhanced diagnoses and alertness to AK, and decreased quality of water in certain localities.
5,13,15,21 The time span for both keratitis outbreaks overlapped (2004–2007), and epidemiologic evidence has shown each was associated with the use of a single but different MPS with “topping-off” as a common risk factor.
1,8 We relate “topping off,” in part, as a response to evaporation of the MPS.
Trophozoites are considered the infective stage of
Acanthamoeba with chronic and recurrent AK related, in part, to differentiation to cysts within cornea tissue.
19,49 The infectious dose of trophozoites for contact lens–related AK in the United States is unknown, but AK may involve, in part, repeated exposure to high numbers of cysts and trophozoites from contact lens storage cases co-contaminated with bacteria and fungi.
8,19,25,48 Several investigations have reported bacterial contamination of lens storage cases to be common (>20%), with
Acanthamoeba being recovered from 8% or more of the cases.
31,50,51 Still, AK remains a rare disease, probably because of the common occurrence of antibodies for
Acanthamoeba in the general population.
19,21,52 The two major upswings in AK in the United States among contact lens wearers were associated in the mid-1980s with the use of home-prepared and nonpreserved saline and in 2006–2007 with use of CMP.
3,5,8,53 These outbreaks may both have been related more to sustained cysts of
Acanthamoeba in contact lens cases than exposure to environmental sources of trophozoites or cysts (
Fig. 9).
In summary, the characteristics of certain drying MPS residues in and on contact lens cases may be significant risk factors for the development of microenvironments that sequester or harbor rare agents of infections. We present and review data that show survival of fusaria on and in cases with RML and the rapid development and aggregation of mature cysts in CMP, the dried residues of which often encapsulate the cysts. Such interactions of drying residues of certain MPSs with some strains of Fusarium and Acanthamoeba suggest that some contact lens case cleaning and replacement recommendations be modified. The generally recognized need for frequent replacement of lens cases is further supported.
We thank Jie Zhang for technical aid provided during the course of this investigation.