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The anatomy and physiology of the ocular adnexa offer several defense mechanisms against offending microbes. To name a few: strong epithelial tight junctions that form a barrier to microbial penetration; the blink reflex, which helps rid the tear film of debris and contaminants; and biochemical properties of the tear film that offer both direct and indirect antimicrobial action.
Some bacterial species have the ability to adhere to and invade an intact cornea, but most corneal infections are opportunistic in nature. Gram-negative species includes Haemophilus egyptius, Neisseria gonorrhoeae, and Neisseria meningitides. The gram-positive species are Corynebacterium diphtheriae and Listeria monocytogenes.
Although there are a number of risk factors for developing microbial keratitis (MK), the most significant modifiable risk factor is contact lens wear.1
Contact lens wear is associated with a risk of vision loss secondary to MK.2,3 Since the introduction of soft contact lenses in 1971, researchers have noticed an increase in the prevalence of this condition.4 MK affects more than 30,000 patients in the United States each year,5,6 and approximately 65% of these cases are associated with soft contact lens wear.7 The risk is highest amongst those choosing to wear their lenses on an extended or overnight basis.3,8
Although the majority of cases in North America are caused by bacteria, we may be seeing an upward trend in contact lens-related fungal infections. According to some reports, contact lens wear has surpassed trauma as the more likely contributing factor in fungal keratitis.9-11
This article reviews the pathogens most commonly associated with contact lens-related MK (CLMK).
Roughly 90% of MK cases in the United States are caused by bacteria.12 Gram-negative bacteria are the predominant cause of CLMK, with Pseudomonas aeruginosa the most commonly isolated organism.13 This especially holds true in regions with a more tropical climate.14 In more temperate regions, gram positive organisms such as Staphylococcus aureus and coagulase- negative staphylococci have been appearing in increasing numbers.15,16
Pseudomonas is a ubiquitous environmental gram-negative bacteria with a strong propensity for adhesion to soft contact lens materials and storage cases. These organisms have a hydrophobic cellular surface coupled with appendages (pili and flagella) that increase their ability to adhere to and penetrate the matrices of both hydrogel and silicone hydrogel lenses. Pseudomonas is more hydrophobic than Staphylococcus, which may be one reason why Pseudomonas shows irreversible adhesion at a much faster rate than staphylococci. The adhesion of S epidermis to soft hydrogel materials occurs incrementally over a couple of hours.17 P aeruginosa, on the other hand, may become irreversibly attached in as quickly as 5 minutes, and most always within 1 hour.
Once adherence occurs, biofilm formation begins. Additional irreversible bonds are formed by excreted polymeric substances that form an adhesive matrix. The biofilm community matures through cellular division as well as microbial recruitment of both similar and diverse species via quorum sensing. Within 24 hours, Pseudomonas can facilitate the development of a mature and diverse (differing bacteria, fungi, and/ or amoebae) biofilm providing enhanced protection against external threats such as disinfection solutions and antimicrobials. From here, spread occurs through segmented dispersion of the biofilm matrix, allowing new colonies to form.
These colonies can spread from one material to another (eg, storage case to contact lens) even in the presence of a multipurpose disinfection solution. This emphasizes the importance of routine cleaning and replacement of contact lens storage cases. Gram-negative biofilms have a propensity to form at the inner upper rim of the case, at the air-liquid interface. Lens cases often show greater levels of contamination than either the contact lens itself or the solution residing within the case.18
It has been proposed that organisms with greater surface hydrophobicity prefer to adhere in greater numbers to lens materials that are more hydrophobic in nature (eg, silicone hydrogel lenses such as lotrafilcon A, balafilcon A, or lotrafilcon B), whereas hydrophilic bacteria adhere well to hydrophilic lenses.19 Similarly, multiple in vitro studies indicate that S aureus and S epidermis have a greater propensity to adhere to silicone hydrogel materials than to hydrogel materials.17,20,21
This likely explains why clinicians and researchers have not seen a decline in the incidence of MK since the introduction of silicone hydrogel lenses in 1999. It was believed that, with improved oxygen transmissibility and, hence, less corneal hypoxia, the incidence of MK related to silicone hydrogel contact lens wear would decrease. This has not been the case.22
Fungal keratitis accounts for 6% to 35% of MK in the United States, with a higher prevalence in tropical climates. It has historically been associated with traumatic injury from organic or vegetative matter.23,24 Recent investigation, however, indicates that fungal infections may be on the rise even in colder, more temperate climates. A retrospective analysis found that soft contact lens wear was the most significant risk factor for fungal keratitis and that filamentous fungi now account for the most fungal keratitis cases.10
Fusarium mold has consistently been the most common filamentous fungus identified in the United States, while Candida is the most common yeast pathogen.25
Fungal keratitis can be very difficult to diagnose. The classic presentation of fungal MK is that of a dull grey, dry, and roughly textured cornea with epithelial heaping in a branched feathery pattern (Figure). Unfortunately, fungal MK may also resemble advanced bacterial MK, either in isolation or as part of a polymicrobial event.
Acanthamoeba is a free-living, ubiquitous protozoa that is a rare cause of MK. According to the Centers for Disease Control and Prevention, there are a reported 1 to 33 cases per 1 million contact lens wearers annually. When cases are reported, contact lens wear is associated with the infection 85% of the time. While rare, Acanthamoeba keratitis (AK) has not shown the same favorable percentage decline as seen with Fusarium, after respective outbreaks (2004 and 2007, respectively) and after the implicated multipurpose solutions were recalled.26,27
When confronted with a nonspecific keratitis showing progression over time despite treatment, or when symptoms of severe pain far exceed the clinical presentation, AK should move to the forefront of the differential diagnosis. It is prudent to question patients with this presentation about certain behaviors or situations associated with AK:
- Swimming, showering, or hot-tubbing while wearing contact lenses;
- Topping off older, possibly contaminated disinfection solution;
- Using homemade saline or tap water-based solutions;
- Coming into contact with contaminated water;
- Having a history of corneal trauma.
While there is no classic presentation of AK, it is often mistaken for herpes simplex keratitis due to the epithelial irregularity and perineural infiltrates. In the early stages one might see pleomorphic epitheliopathy and punctate erosions. Epithelial defects are uncommon early in the disease process. A nonsuppurative ring infiltrate and radial neuritis are more common in the intermediate stage of AK. If there is a delay in diagnosis and treatment, progression to late stage disease (thinning, perforation, and opacification) are likely to ensue.
In recent years there has been growing research geared toward the prevention of CLMK. Whether it is the study of covalently binding melamine into contact lens materials,28 attempts to bind selenium into propylene injection-molded contact lens cases, or the development of broader spectrum dual disinfection solutions, there is a clear understanding that the best way to prevent vision loss from CLMK is to prevent the infection in the first place.
Most of the pathogens discussed above can be challenging to eradicate without collateral tissue damage, especially if there is a delay in diagnosis or treatment. Central corneal ulcers that are fungal or protozoan in nature typically carry a poor prognosis, and management often includes corneal transplantation. Additionally, ARMOR (Antibiotic Resistance Monitoring in Ocular Microorganisms) surveillance data presented at this year’s Association for Research in Vision and Ophthalmology meeting indicate increasing levels of resistance in Pseudomonas, S aureus and coagulase-negative staphylocci when compared with the previous year, with staphylococcal pathogens showing multidrug resistance approximately 40% of the time.
What is the answer? According to a 2011 survey, the majority of contact lenses prescribed in the United States today are silicone hydrogel lenses, with daily disposables accounting for roughly 19% of new fits.30 Studies show that 40% to 70% of those who choose to wear soft contact lenses are noncompliant with some aspect of their prescribed wearing, cleaning, or disinfection protocol. Switching to daily disposable wear reduces the risk of bacterial adherence from contaminated solutions or cases. Daily disposable wear does not completely eliminate the risk of lens contamination or MK, but it is associated with a significant decline in CLMK-related vision loss when compared with lenses replaced less frequently.3,31
Although the cost associated with these lenses may be a barrier for some, the quality of vision, comfort, and ocular health benefits realized from daily disposable lenses should be emphasized to every candidate. Promoting daily disposable wear may help to keep CLMK out of your chair.
Richard B. Mangan, OD, practices at Bennett & Bloom Eye Centers in Louisville, Kentucky. Dr. Mangan may be reached at (859) 321- 0037; firstname.lastname@example.org.
- Green M, Apel A, Stapleton F. Risk factors and causative organisms in microbial keratitis. Cornea. 2008;27(1):22-27.
- Garg P. Diagnosis of microbial keratitis. Br J Ophthalmol. 2010;94:961-962.
- Stapleton F, Keay L, Edwards K, et al. The incidence of contact lens-related microbial keratitis in Australia. Ophthalmology. 2008;115:1655-1662.
- Fleiszig SM, The Glenn A. Fry award lecture 2005. The pathogenesis of contact lens-related keratitis. Optom Vis Sci. 2006;83:866-873.
- Jeng BH, Gritz DC, Kumar AB, et al. Epidemiology of ulcerative keratitis in Northern California. Arch Ophthalmol. 2010;128:1022-1028.
- Hsu HY, Nacke R, Song JC, et al. Community opinions in the management of corneal ulcers and ophthalmic antibiotics: a survey of 4 states. Eye Contact Lens. 2010;36:195-200.
- Jeng BH, Mcleod SD. Microbial keratitis: shifting trends in the epidemiology of infectious keratitis demand that we approach all cases thoughtfully. Br J Ophthalmol. 2003;87:805-809.
- Yeung KK, Forister JF, Forister EF, et al. Compliance with soft contact lens replacement schedules and associated contact lens-related ocular complications: The UCLA Contact Lens Study. Optometry. 2010;81:598-607.
- . Srinivasan M. Fungal keratitis. Curr Opin Ophthalmol. 2004;15:321-327.
- Jurkunas U, Behlau I, Colby K. Fungal keratitis: changing pathogens and risk factors. Cornea. 2009;28:638-643.
- Yildiz EH, Abdalla YF, Elsahn AF, et al. Update on fungal keratitis from 1999 to 2008. Cornea. 2010;29:1406-1411.
- Musa F, Tailor R, Gao A, et al. Contact lens-related microbial keratitis in deployed British military personnel. Br J Ophthalmol. 2010;94:988-993.
- Cheng KH, Leung SL, Hoekman HW, et al. Incidence of contact-lens associated microbial keratitis and its related morbidity. Lancet. 1999;354:181-185.
- Houang E, Lam D, Fan D, Seal D. Microbial keratitis in Hong Kong: relationship to climate, environment and contact-lens disinfection. Trans R Soc Trop Med Hyg. 2001;95:361-367.
- Wahl JC, Katz HR, Abrams DA. Infectious keratitis in Baltimore. Ann Ophthalmol. 1991;23:234-237.
- Tabbara KF, El-Sheikh HF, Aabed B. Extended wear contact lens related bacterial keratitis. Br J Ophthalmol. 2000;84:327-328.
- George M, Ahearn D, Pierce G, Gabriel M. Interactions of Pseudomonas aeruginosa and Staphylococcus epidermidis in adhesion to a hydrogel. Eye Contact Lens. 2003;29:S105-109.
- Wu YT, Zhu H, Harmis NY, et al. Profile and frequency of microbial contamination of contact lens cases. Optom Vis Sci. 2010;87:153-158.
- Vermeltfoort PB, Rustema-Abbing M, de Vries J, et al. Influence of day and night wear on surface properties of silicone hydrogel contact lenses and bacterial adhesion. Cornea 2006; 25:516-523.
- Bruinsma GM, van der Mei HC, Busscher HJ. Bacterial adhesion to surface hydrophilic and hydrophobic contact lenses. Biomaterials. 2001;22:3217-3224.
- Henriques M, Sousa C, Lira M, et al. Adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to silicone-hydrogel contact lenses. Optom Vis Sci. 2005;82:446-450.
- Willcox M. Microbial adhesion to silicone hydrogel lenses. Eye Contact Lens. 2013;39(1):61-66.
- Alfonso EC, Forster RK, Garg P, et al. Fungal infections. In: Foster CS, Azar DT, Dohlman CH, eds. Smolin and Thoft’s The Cornea Scientific Foundations & Clinical Practice. 4th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005:405-416.
- Liesegang TJ, Forster RK. Spectrum of microbial keratitis in South Florida. Am J Ophthalmol. 1980;90(1):38-47.
- Embong Z, Wan Hitam WH, Yean CY, et al. Specific detection of fungal pathogens by 18S rRNA gene PCR in microbial keratitis. BMC Ophthalmol. 2008;8:7.
- Yoder JS, Verani J, Heidman N, et al. Acanthamoeba keratitis: The persistence of cases following a multistate outbreak. Ophthalmic Epidemiol. 2012;19(4):221-225.
- Brown AC, Ross J, Yoder J, et al. Elevated Acanthamoeba keratitis incidence despite a 2007 outbreak associated product recall: a multi-state investigation, 2008-2011. Paper presented at: Epidemic Intelligence Service Conference; April 16-20, 2012; Atlanta.
- Dutta D, Ozkan J, Willcox MD. Biocompatibility and retention of activity of melamine antimicrobial contact lenses in a human clinical trial. Poster presented at: Association for Research in Vision and Ophthalmology Annual Meeting; May 4-8, 2014; Orlando, FL.
- Morgan P, Efron N, Woods C. Contact lens prescribing: USA vs. the world. Review of Cornea and Contact Lenses. June 15, 2012.
- Sanfilippo CM, Morris TW, Deane J, et al. Antibiotic Resistance Profile of Ocular Pathogens – An update from the 2013 US ARMOR Surveillance Study. Poster presented at: Association for Research in Vision and Ophthalmology Annual Meeting; May 4-8, 2014; Orlando, FL.
- Dart JK, Radford CF, Minassian D, Verma S, Stapleton F. Risk factors for microbial keratitis with contemporary contact lenses: a case-control study. Ophthalmology. 2008;115(10):1647-1654.