Optometry & Vision Science

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Optometry & Vision Science:
doi: 10.1097/OPX.0b013e3181eedde2

Pathogenesis of Contact Lens-Associated Microbial Keratitis

Carnt, Nicole BOptom; Willcox, Mark D. P. PhD; Keay, Lisa PhD; Flanagan, Judith PhD; Stapleton, Fiona PhD, FAAO

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Brien Holden Vision Institute, School of Optometry and Vision Science, University of New South Wales, Sydney, Australia (Carnt, Willcox, Stapleton)

School of Optometry and Vision Science, University of New South Wales, George Institute for International Health, University of Sydney, Sydney, Australia (Keay)

University of New South Wales, Sydney, Australia (Flanagan)

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Sir, we refer to the recent article of Fleiszig and Evans1 in which they present an informative appraisal of the pathogenesis of contact lens-associated microbial keratitis.

The authors raise a concern that emphasis on compliance should not take priority in efforts to reduce microbial keratitis because this might decrease the effort directed toward understanding the etiology of this serious adverse event. These two processes are by no means mutually exclusive. The authors indicate that poor compliance by the contact lens wearer is not always a significant risk factor for microbial keratitis. However, the link between various aspects of compliance and infection has been very clearly articulated in well-designed epidemiological studies.2

It has been estimated that if hygiene were improved, approximately one third of all disease could be eliminated.3 Various aspects of compliance including hand washing, disinfection frequency, topping off, case hygiene, and overall disinfection score have been examined in relation to microbial keratitis, and one or more of these appears in the majority of well-conducted epidemiological studies. As an aside, the statement that “scare tactics such as graphic images of infections may not help, considering that horrific photos on cigarette packs have had little impact on smoking” is not in agreement with the link between graphic images on cigarette packaging and decreases in smoking.4 Although smoking is inherently harmful and not a good analogy for contact lens wear, encouraging responsible contact lens use can be effective in minimizing risk of infection. Prevention or reduction of biofilms and adherent organisms on lens surfaces is desirable in an effort to reduce the incidence of microbial adverse events and thus the drive to increased compliance must be part of the overall strategy along with technological advances.

The authors' statement “low efficacy of certain disinfection solutions (rather than non-compliance) was implicated in the Fusarium spp. and Acanthamoeba spp. keratitis outbreaks in lens wearers” does not accurately reflect the observations arising from investigations into the failure of, e.g., ReNu Moistureloc (Bausch and Lomb) disinfecting solution that implicated both disinfecting efficacy and patient compliance. Although the solutions in question met the ISO Stand Alone disinfection criteria and were reported as being efficacious,5 it is suggested that a combination of the novel ingredients, and a degree of non-compliance by users caused the increase in Fusarium keratitis.6 Simulating evaporation of ReNu MoistureLoc reduced its disinfecting power against Fusarium sp.7 “Topping off” instead of replacing solution used previously to disinfect lenses, resulted in conditions similar to evaporation. Manufacturers have for some years, recommended discarding used solutions and drying lens cases between disinfecting cycles.

In relation to lack of an adequate animal model; dismissal of the use of contact lenses on larger animals (rabbits) because of fitting issues and expense and consequent lack of data for statistical analysis, fails to acknowledge that several publications have successfully used larger animals (rabbits or guinea pigs) with properly designed lenses that fit adequately, to achieve statistically significant effects as early as 1988.8 In 1994, Solomon et al.9 demonstrated that contact lenses could be fitted to rabbit eyes and used as an inoculum to produce bacterial keratitis. Vijay et al.10 and Wu et al.11 used lenses specially designed to fit the eyes of guinea pigs or rabbits to produce models of acute keratitis. Hazlett et al.12 and Sankaridurg et al.13 used contact lenses fitted to rabbit eyes to demonstrate recruitment of Langerhan's cells into the cornea during lens wear. Cole et al.14 have used lenses designed for both rabbit and guinea pig eyes to demonstrate the effectiveness of an antimicrobial lens to reduce the production of bacterially driven adverse events in corneas. Zhu et al.15 used lenses designed to fit guinea pig eyes to show the safety of another type of antimicrobial contact lens. These studies may be more expensive than using rats or mice, but they are feasible and yield statistically significant findings.

The discussion of antimicrobial lenses by Fleiszig and Evans suggests that all bactericidal lenses would engender resistance in targeted bacteria. This is certainly not the case. It is generally accepted that there is a low probability of development of bacterial resistance to silver.16 Genes that mediate resistance to silver are known to occur in bacteria, although these genes have only been found infrequently and even when present, silver-containing wound dressings were able to reduce bacterial growth after 24 hours exposure.17 The presence of silver may even reduce resistance to conventional antibiotics.18

The authors' discussion fails to mention that in many studies examining the attachment/adhesion of microbes to contact lenses, Pseudomonas aeruginosa has generally been shown to adhere, at least initially, in higher numbers (up to a fold difference) to lenses than other bacterial genera/species.19 This may equally be a reason for the over representation of this bacteria in the pathogenesis of microbial keratitis.

In conclusion, Fleiszig and Evans have presented an informative article relating to the pathogenesis of microbial keratitis. We agree with the authors that it is of critical importance that industry, practitioners, and patients cooperate in their efforts to reduce the incidence of this potentially sight threatening adverse event. However, the authors appear rather dismissive of possible gains through responsible contact lens use in the community. Further, their suggestion that complications can be solved with a product or new knowledge, with the further assertion that emphasis on compliance somehow detracts from these efforts, is a cause for concern. Animal models, use of antimicrobial lenses and patient education in compliance all have significant roles to play in our efforts to reduce the incidence of microbial keratitis.

Nicole Carnt, BOptom

Mark D. P. Willcox, PhD

Brien Holden Vision Institute

School of Optometry and Vision Science

University of New South Wales

Sydney, Australia

Lisa Keay, PhD

School of Optometry and Vision Science

University of New South Wales

George Institute for International Health, University of Sydney

Sydney, Australia

Judith Flanagan, PhD

University of New South Wales

Sydney, Australia

Fiona Stapleton, PhD, FAAO

Brien Holden Vision Institute

School of Optometry and Vision Science

University of New South Wales

Sydney, Australia

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1.Fleiszig SM, Evans DJ. Pathogenesis of contact lens-associated microbial keratitis. Optom Vis Sci 2010;87:225–32.

2.Stapleton F, Keay L, Jalbert I, Cole N. The epidemiology of contact lens related infiltrates. Optom Vis Sci 2007;84:257–72.

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8.Dart JK, Peacock J, Grierson I, Seal DV. Ocular surface, contact lens and bacterial interactions in a rabbit model. J Brit Contact Lens Assoc 1988;11(Suppl.):95–7.

9.Solomon OD, Loff H, Perla B, Kellis A, Belkin J, Roth AS, Zucker J. Testing hypotheses for risk factors for contact lens-associated infectious keratitis in an animal model. CLAO J 1994;20:109–13.

10.Vijay AK, Sankaridurg P, Zhu H, Willcox MD. Guinea pig models of acute keratitis responses. Cornea 2009;28:1153–9.

11.Wu PZ, Thakur A, Stapleton F, Willcox MD. Staphylococcus aureus causes acute inflammatory episodes in the cornea during contact lens wear. Clin Experiment Ophthalmol 2000;28:194–6.

12.Hazlett LD, McClellan SM, Hume EB, Dajcs JJ, O'Callaghan RJ, Willcox MD. Extended wear contact lens usage induces Langerhans cell migration into cornea. Exp Eye Res 1999;69:575–7.

13.Sankaridurg PR, Rao GN, Rao HN, Sweeney DF, Holden BA. ATPase-positive dendritic cells in the limbal and corneal epithelium of guinea pigs after extended wear of hydrogel lenses. Cornea 2000;19:374–7.

14.Cole N, Hume EB, Vijay AK, Sankaridurg P, Kumar N, Willcox MD. In vivo performance of melimine as an antimicrobial coating for contact lenses in models of CLARE and CLPU. Invest Ophthalmol Vis Sci 2010;51:390–5.

15.Zhu H, Kumar A, Ozkan J, Bandara R, Ding A, Perera I, Steinberg P, Kumar N, Lao W, Griesser SS, Britcher L, Griesser HJ, Willcox MD. Fimbrolide-coated antimicrobial lenses: their in vitro and in vivo effects. Optom Vis Sci 2008;85:292–300.

16.Muhling M, Bradford A, Readman JW, Somerfield PJ, Handy RD. An investigation into the effects of silver nanoparticles on antibiotic resistance of naturally occurring bacteria in an estuarine sediment. Mar Environ Res 2009;68:278–83.

17.Woods EJ, Cochrane CA, Percival SL. Prevalence of silver resistance genes in bacteria isolated from human and horse wounds. Vet Microbiol 2009;138:325–9.

18.Fayaz AM, Balaji K, Girilal M, Yadav R, Kalaichelvan PT, Venketesan R. Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics: a study against gram-positive and gram-negative bacteria. Nanomedicine 2010;6:103–9.

19.Kodjikian L, Casoli-Bergeron E, Malet F, Janin-Manificat H, Freney J, Burillon C, Colin J, Steghens JP. Bacterial adhesion to conventional hydrogel and new silicone-hydrogel contact lens materials. Graefes Arch Clin Exp Ophthalmol 2008;246:267–73.

© 2010 American Academy of Optometry


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