The patient was seen by staff at Western Hospital Ophthalmology on May 22, 2009. Her presenting visual acuity with spectacle correction for distance was 20/20 OD and OS. Pupils were equal and reactive to light and accommodation. Slit lamp examination revealed a small corneal infiltrate with mild staining overtop. There was marked improvement in the patient's condition and the dose of Vigamox was subsequently reduced to one drop four times daily for five days. The small ulcer was attributed to contact lens noncompliance, and she was instructed not to wear contact lenses until her follow-up in one week.

The patient returned to Western Hospital Ophthalmologist on June 15, 2009. (Unclear is why, after one week, the patient had not returned as scheduled.) The attending ophthalmologist instructed the patient never to sleep in her contact lenses and informed the patient of the risks of contact lens noncompliance. The examination was unremarkable, and “eyes all clear” was written in the record. Neither was the ulcer present nor were the symptoms of discharge, redness and pain from the first visit.

Although progressive research continues to make inroads into a fuller understanding of the mechanism of ulceration,20 several factors play a role in contact-lens-related keratitis. They include bacterial adherence to the lens, formation of biofilm on the lens and in the storage case, resistance of microorganisms to disinfection systems, stagnation of tear film behind contact lenses and reduced resistance of the cornea to infection.9,20

In bacterial keratitis, bacteria accessing the corneal stroma cause damage and an inflammatory response which result in loss of transparency.3 Although some bacteria can invade a healthy cornea, most enter through either an abnormality or a defect in the corneal surface.10

Corneal ulceration is mercifully less common than the presence of bacteria on ocular surfaces.11,20 Clearly, under normal conditions, the cornea's countermeasures are highly effective against invaders.3,20 Hypoxia may increase bacterial binding, compromise corneal integrity and impair wound healing.4 These effects are reduced but not eliminated with silicone hydrogel lenses.9 Hypoxia, which is unlikely to be the sole factor in corneal ulceration, is most likely a contributor.3

Changes to ocular surface biochemistry underneath the contact lens may be why contact lens wearers are more susceptible to infection.20 Interaction with contact lenses can override the cornea's defence mechanism and increase the rate at which pathogens adhere to the ocular surface and allow progression to microbial keratitis.9,17,20 The adhesion of bacteria to contact lenses is considered a major risk factor for serious corneal problems (particularly Staphylococcus epidermis and Pseudomonas aeruginosa).17,20 Contact lenses are a suitable surface for bacterial adhesion and biofilm formation.20 They sustain a large quantity of organisms in prolonged contact with the cornea.9,17 Rougher contact lenses surfaces are prone to more extensive bacterial adhesion and microbial colonization from imperfections in the lens surface, where deposits may form.17

Gram negative bacteria may survive at the upper inner rim of the case where, due to the air-liquid interface, biofilms have a higher likelihood of occurring.7 Therefore, a patient making contact with that area of the case while handling a lens before its insertion may be severely reinfecting the lens.7

Contamination of the contact lens case has been associated with microbial keratitis.9 The case has been shown to be more heavily contaminated than either lens or solution.7 The same strains have been isolated from a corneal ulcer and the contact lens case.7 Level of contamination is associated with the age of the lens case.4

The elimination of “rub and rinse” may decrease the amount of microorganisms removed in the cleaning process and create a “carry-over effect” (from lens to case) which allows the remaining pathogens to form a biofilm in the case and to increase their virulence and rate of survival.7,9,10,20

Contact lens wear seems to reduce tear exchange; the mean elimination rate in eyes wearing conventional contact lenses is about half of that observed in normal non-wearers of contact lenses.9,20 However, silicone hydrogels may allow significantly higher levels of tear exchange than conventional lenses.21 The impact of tear exchange on the risk of microbial keratitis is not fully understood.3,20,21

Risk of contact lens microbial keratitis varies widely with the type of contact lens and pattern of wear.10 The rate of progression of microbial keratitis is dependent on the virulence of the offending pathogen and host factors.10,11Pseudomonas aeruginosa, one of the more common pathogens in CLMK, is highly destructive and difficult to neutralize because of its virulent structure, adaptability and high rate of survival under different conditions.3,20 Another highly common pathogen in CLMK, staphylococcus, may account for 45% of all bacterial keratitis.11,17

Because no clinical features of microbial keratitis may be considered pathognomonic, the identification of the pathogen is critical.1 In the U.S., the most common practice begins treatment empirically and only investigates the offending pathogen if initial treatment fails.1,2,10 One U.S. study has shown that approximately half of American ophthalmologists routinely culture and only 17.5% gram stain.16 The same study showed that only 13% perform cultures more than fifty per cent of the time.16

A restrained approach to cultures may be justified when we consider that over 90% of ulcers in the U.S. are bacterial in nature and respond to antibiotics.2 The policy that all ulcers be cultured before treatment be initiated is, for practical reasons of time and cost, not followed by most specialists.2,22 Before initiating treatment, cultures are indicated in either sight-threatening or severe keratitis.10 Smears and cultures are indicated either when the infiltrate is large, when it is central, when there is no response to broad spectrum antibiotics or when the observation of atypical clinical features suggests a more exotic pathogen (such as either fungus or acanthamoeba).10,18

Cultures can also decrease toxicity by eliminating the use of unhelpful medications.10 Culture yields can be improved by avoiding anaesthetics with preservatives.10 Cultures of either the contact lens, its case or the solution may also be helpful.10,18 The best approach is to culture and to treat lesions as potentially infective.22

CLMK is assumed to be bacterial until proven otherwise.12,18 The goal of treatment is the rapid eradication of the pathogen.1 Currently the “gold standard” of treatment for corneal ulceration is the use of fortified antibiotics: either cefazolin 5% and tobramycin 1.3% or monotherapy with second generation fluoroquinolones (either ciprofloxacin or ofloxacin).8,19

Frequency of re-evaluation depends on severity of disease but microbial keratitis should initially be monitored on a daily basis.10,12 If pain decreases and the epithelial defect, infiltrate size and anterior chamber reaction improve, the treatment may be considered to be effective.18

Treatment should be re-evaluated after 48 hours if there is no sign of improvement (although pseudomonas and other gram negative bacteria may show increased inflammation despite appropriate therapy within the first 24 to 48 hours).10 When ulcers are either atypical or unresponsive to medication, a mixed bacterial and fungal infection should be considered.11 Ciprofloxacin ointment at bedtime (optionally tobramycin in less severe cases) may be useful.18 Cycloplegic drugs decrease synechia formation, reduce pain and manage anterior chamber reaction.12,13

While some experts advocate the use of topical corticosteroids in concert with topical antibiotics,22 the value of topical steroids remains controversial.12,13 There is no conclusive evidence that corticosteroids alter clinical outcome.10,13 Consequently, the amount of corticosteroids used to achieve control of inflammation should be minimized.10 Subconjunctival antibiotics may be used in patients with poor compliance with topical treatment.13 Systemic antibiotics are rarely used but may be considered for severe infections.10,13

Keratoplasty may be considered when aggressive microbial keratitis doesn’t respond to medical therapy.11,18 The procedure aims to eliminate the infectious disease process and to establish the integrity of the globe.11,23 The procedure offers a microbial cure rate of 90 to 100%.23 With the emergence of more potent antimicrobial agents, therapeutic keratoplasty is required less often.23 A recent study in Bahrain found that only 1% of CLMK patients needed therapeutic keratoplasty.6

After their introduction in the 1990s, second generation fluoroquinolones quickly became an accepted alternative to fortified antibiotics.16 Ciprofloxacin was the most frequently used topical medication –prescribed to approximately 90% of patients in the Portsmouth study.14

Relative ease of dosing and higher potency are among the factors increasing interest in fourth generation fluoroquinolones, which are also without the recent resistance some bacteria have developed to Ciloxan (ciprofloxacin) and Ocuflox (ofloxacin).8,10 The suggested initial dose of either Vigamox (moxifloxacin) or Zymar (gatifloxacin) is one drop every one to two hours.12,18 In less severe cases, a regime with less frequent dosing is appropriate.10

Moxifloxacin and gatifloxacin both have improved potency and impede growth of organisms resistant to the second and third generation antibiotics.8,10,19 In a recent study, moxifloxacin and gatifloxacin were found to have lower minimum inhibitory concentrations (MIC) than fortified antibiotics and second generation fluoroquinolones.8 The inhibitory property of DNA topoisomerase IV reduces the likelihood that pathogens shall develop resistance to moxifloxacin and gatifloxacin.8,10 Fourth generation fluoroquinolones require two mutations to establish resistance while the second generation only needs one mutation for resistance to occur.19 They have better penetration of the cornea and aqueous and therefore may lead to more effective therapeutic levels and better prognosis.8

One study by Hsu et al. has found that corneal specialists and comprehensive ophthalmologists by overwhelming majority (76% and 88% respectively) use fourth generation fluoroquinolones as the initial treatment of choice in corneal ulcers.16 Several studies have found no difference in efficacy between the fourth generation fluoroquinolones and the generally accepted alternatives.8,19 Emerging evidence of resistance to fourth generation fluoroquinolones is isolated,8 and they can therefore be considered just as effective as, if not more effective than, the currently accepted treatments.10,12,13,16,18,19 However, fourth generation fluoroquinolones are not yet FDA-approved for treatment of bacterial keratitis.8,10

The problem of contact lens care is a common one; studies suggest that 40 to 70% of patients are noncompliant.24 Healthy contact lens wear depends on many factors. They include age, sex, lens brand, smoking habits, cleaning regime and wearing regime.25 Higher rates of complications were associated with men, with youth, with smokers, with longer periods of wear and with a lack of hand-washing.7,17,24,25 (Internet purchase, possibly due to attitudes and behaviours associated with it, was also recently identified as a risk.)4

Noncompliance with the manufacturer's recommended frequency of replacement of contact lenses is highest among teenagers and among the wearers of non-silicone hydrogels.24

Microbial contamination of contact lens case and poor contact lens hygiene are also associated with microbial keratitis.4 Recent studies also suggest noncompliance is a factor in corneal infections related to CL solution.24 Patients using hydrogen peroxide solutions were found to be more compliant with the contact lens replacement schedule, perhaps because the care regime is more complex and demanding.24

Daily disposables were found to be associated with the lowest rate of complications in general.24 They also have lower risks for severe CLMK and associated vision loss.4,20 Because neither a case nor a cleaning regime is at issue with daily disposables, their use may both reduce the risk of microbial keratitis and decrease its severity.4,7 Studies suggesting that daily wear decreased the risk of microbial keratitis remain controversial.9,15,20,26

Early treatment can limit the scarring and vision loss caused by CLMK.8,27 Even a slight delay in assessment and treatment can increase the risk of a poorer outcome.11,25 Recent studies show that treatment delayed by more than 12 hours increases the risk of vision loss.9 Therefore, timely recognition and treatment is of paramount importance.1,10 This would suggest that countries should follow the American model and expand the scope of practice of optometrists to enable more immediate access to crucial care.25

Although the risk to the individual is low, the group at risk is a vital one, including the young, healthy and of working age who are at low risk of infection in the absence of overnight contact lens wear.4,6,9 Though lenses may be approved for overnight wear, informing patients of the associated risks of such use may decrease the incidence of corneal ulcers.15 Risks include the destructive nature of microbial keratitis and the potential for rapid, painful and permanent vision loss.10,27 There is evidence that overnight contact lens wearers are at greater risk of microbial keratitis especially in the early days of their wear experience.4 Patients should be particularly cautioned never either to sleep or to nap in their contact lenses.10 Teenaged and young adults should be especially educated on proper contact lens procedures and the potential for complications. Demographically common behaviours such as poor hygiene, binge drinking and contact lens overuse put them at higher risk.25

Confocal microscopy is a promising tool in the diagnostic arsenal and may be used in the differential diagnosis of infectious keratitis, particularly where it involves acanthamoeba and fungus.1,10,12

Collagen crosslinking (CXL) with riboflavin and ultraviolet-light A, has been used successfully to halt the progression of Keratoconus28,29 by increasing the biomechanical strength of the tissue and has shown potential as a treatment for severe cases of bacterial keratitis29,30,31,32. Photoactivation of riboflavin (a naturally occurring vitamin32,33) is thought to damage the RNA and DNA of bacteria, viruses and parasites31,33 and to inactivate them.29,31,32,33 CXL may also increase the collagen defence against enzymatic degradation.29 This technique could potentially be used as an alternative to keratoplasty when uclers do not respond to either systemic or topical therapy.29,30,31 A crosslinked cornea is also more resistant to corneal melting.31 Further investigation is needed to determine the ideal role of corneal crosslinking in the treatment of bacterial keratitis.29,31 The use of this technique is not yet widespread.32 Due to possible cytotoxic effects, CXL should be considered only in keratitis resistant to therapy and not as a first line of treatment.29

Better lens storage design, frequent replacement of the case (every 3 to 6 months) and improved hygiene may decrease the incidence of corneal ulceration.7 Rubbing contact lenses when cleaning should be encouraged because that method may be superior to the “no rub” alternative.9,10,34

A recent study by Hua Zhu et al. found that “rub and rinse” removed bacteria more effectively than did rinsing alone, without regard to either the multipurpose solution used or the type of contact lens.34 Interestingly, with “rinse only” multipurpose disinfection, a regime containing Polyquad solution removed more bacteria than did those with PHMB (polyhexamethylene biguanide), and Gatyfilcon was more resistant to bacterial adhesion (with rinse only) than were other silicone hydrogel lenses.34

A better understanding of the mechanism behind microbial keratitis will help eye care professionals to recommend and ultimately to create better lenses and to suggest ways to decrease the risks.20 For the present, the fitting of patients in silicone hydrogels and daily disposables while absolutely advocating against sleeping in the lenses appears to be the best form of prevention.