**4. Etiology**

CLAIK is mainly attributed to bacterial pathogens with up to 90% of the cases (**Table 1**). Moreover, although fungal and protozoal infections are infrequent, they are more severe [24]. The most common bacterial agent involved in CLAIK is *Pseudomonas aeruginosa,* according to several reports (**Figure 1A** and **B**). Gram-negative bacteria are more frequently isolated in tropical climates. Grampositive bacteria are more commonly identified in regions with temperate climates like Australia and France [2, 3, 11]. Such bacteria include coagulase-negative *Staphylococcus* (including *Staphylococcus epidermidis*), *Staphylococcus aureus,* and *Streptococcus pneumoniae*. *S. aureus* is associated with more severe disease and recurrent infections [25].

On the other hand, keratitis caused by *Acanthamoeba* and fungi has increased in the past few years [26]. In 2006, an outbreak of CLAIK caused by *Fusarium* was first reported in Singapore [27], followed by multiple reports in the United States [28–30]; these outbreaks were directly linked to a particular contact lens solution formulation reported a decreased antifungal activity [31]. In the same year,

*Contact Lens-Associated Infectious Keratitis: Update on Diagnosis and Therapy DOI: http://dx.doi.org/10.5772/intechopen.100261*


**Table 1.**

*Prevalence of causal microorganisms of contact lens-associated infectious keratitis.*

#### **Figure 1.**

*A. The left cornea of a patient with a five day-history of red-eye, discharge, and pain after wearing disposable contact lenses overnight. Conjunctival chemosis and ciliary injection are present; a dense stromal infiltrate, 2 mm hypopyon, and a shallow anterior chamber are observed. B. Fluorescein staining shows an extensive overlying epithelial defect. The smear staining revealed a Gram-negative rod, and the culture confirmed the diagnosis of Pseudomonas aeruginosa.*

outbreaks of *Acanthamoeba* keratitis were also reported and partly associated with another contact lens solution [32].

It is noteworthy to mention the occurrence of CLAIK associated with multiple microorganisms. A retrospective analysis of CLAIK, performed by Karaca et al., demonstrated that 20% (12 cases) were mixed infections. All of them were mixed bacterium-bacterium infections. *P. aeruginosa* was involved in eight cases [33]. Regarding mixed fungi-bacterial infections, Ahn et al. reported a prevalence of 4.4% (33/757). Ocular trauma (45.5%) and diabetes mellitus (18.2%) were the most frequent associated risk factors for mixed bacterial and fungal keratitis, and *Fusarium spp.* and *Staphylococcus spp.* were the most frequent fungi and bacteria isolated, respectively [34].

### **5. Risk factors**

Among the many different risk factors predisposing to CLAIK, overnight wear and poor hygiene are the two most frequent ones, accounting for 43% and 33%


*1 Especially related to Acanthamoeba keratitis.*

*2 High risk when exposure to ocean/sea/river/lake water and highest risk when swimming in public or private pool and hot tub.*

*3 Low socioeconomic status is associated with higher risk of Acanthamoeba keratitis.*

#### **Table 2.**

*Modifiable and non-modifiable risk factors associated with contact lens-associated infectious keratitis.*

of the cases, respectively [35]. Regarding corneal infection in overnight wear, the risk is higher with increased extended wear and inexperienced patients [36, 37]. Interestingly, in severe keratitis, mishandling of the contact lens case (poor hygiene and lack of replacement) accounts for 63% of the population-attributed risk for bacterial and fungal infection. Moreover, swimming with contact lenses on and traveling are also risk factors for infection. The former for *Acanthamoeba* keratitis, and the latter related to routine wearing changes [3, 38].

Other risk factors of infectious keratitis in contact lens wearers include being a male, probably related to poor compliance and reluctance to seek regular care attention [39]. Genetic susceptibility related to small mutations of defensins, interleukins, and other inflammatory mediators seems to play a role in CLAIK (**Table 2**) [43].

### **6. Pathogenesis**

The primary vector for bacterial transmission in CLAIK is the contact lens through various contaminants, including the eyelids, hands, storage case, cosmetics, and contaminated water or lens solutions [44, 45]. Contact lenses wear alone alters the normal physiology of the cornea. To a greater or lesser extent, the local hypoxia induced by contact lenses causes a decreased epithelial metabolic rate, resulting in epithelial thinning, loss of tight cell junctions, and hemidesmosomes,

#### *Contact Lens-Associated Infectious Keratitis: Update on Diagnosis and Therapy DOI: http://dx.doi.org/10.5772/intechopen.100261*

which lead to epithelial abrasions predisposing to opportunistic infections. Other corneal hypoxic effects include vascularization and hypoesthesia.

The understanding of CLAIK pathogenesis has changed over time as contact lens materials evolved. Contact lens wear increased in popularity when soft hydrogel contact lenses were introduced, given a higher comfort for the wearer [46]. However, their intrinsic low-oxygen transmissibility was demonstrated to be problematic. It is well-known that lower oxygen transmissibility is related to a higher rate of bacterial binding to the corneal surface; hypoxic conditions in human corneas increase wild-type cystic fibrosis transmembrane conductance regulator (CFTR) expression, which is the cellular receptor for *Pseudomonas aeruginosa*. Hence a lower bacterial load can induce infectious keratitis and inflammatory responses in this type of contact lenses [47]. Previous reports show that decreasing oxygen permeability of contact lenses is associated with increased desquamation of superficial epithelial cells of the cornea [48–50]. These observations led to development and innovation in contact lens materials to address the problem of hypoxia, which led to the advent of highly oxygen-transmissible, soft silicone hydrogel contact lenses. With the introduction of silicone hydrogel soft contact lenses, a decrease in infectious keratitis cases was anticipated; this was hypothesized because of their increased oxygen permeability and decreased bacterial binding [50]. However, no difference in the incidence of infectious keratitis was observed; clinical characteristics, pathogens, and rate of vision loss also remained unchanged despite the new contact lens material [1].

Because solving the hypoxia mechanism did not result in a reduced incidence rate of microbial keratitis, other alternative pathogenic mechanisms are suggested for corneal infection, including inadequate tear exchange. Deficient tear exchange leads to the entrapment of debris and microbes on the posterior surface of contact lenses and hinders the natural antimicrobial functions of the tear film. In fact, there is a reduction in the antimicrobial activity of the tear film on the posterior surface of silicone hydrogel soft contact lenses after 8 hours of wearing them [51]. This mechanism could explain why soft contact lenses are associated with a higher risk of infectious keratitis than rigid gas permeable lenses, given the inadequate tear exchange in the former [52, 53].

Microbes responsible for infectious keratitis may come from the lid margins, the wearers' fingers upon contact lens insertion, or removal, directly from the contact lens or indirectly from the storage case or the lens care solution [54]. Contact lens case contamination has been reported in up to 80% of contact lens wearers, despite adequate compliance with care regimens [55, 56]. The formation of bacterial biofilm on the contact lens surface and storage cases has been previously reported, and it may also play a role in the pathogenesis of microbial keratitis [56]. Bacterial cells within a biofilm show increased resistance to antimicrobial agents [57]. Moreover, multiple biguanide-based contact lens solutions have no effect against biofilms of *Serratia marcescens, Staphylococcus aureus,* and *Pseudomonas aeruginosa* formed in silicone hydrogel contact lenses [58]. Also, outbreaks of keratitis caused by *Acanthamoeba* and *Fusarium spp* have been linked to specific contact lens solutions [26, 27, 32].

Animal models have also been used to improve understanding CLAIK. In mouse and guinea pig models, a corneal erosion must occur to produce infectious keratitis; animals with non-scratched corneas only show non-infectious inflammatory responses [59]. This has led to the hypothesis that a corneal defect or erosion is a prerequisite for CLAIK to occur and not microbial contamination alone [60]. Corneal erosions are known complications in contact lens wearers, especially on extended wear schedules [61, 62].

#### **Figure 2.**

*Flow chart showing the relationship between the risk factors and the main events involved in the pathogenesis and development of contact lens-associated infectious keratitis.*

Several risk factors have been associated with microbial keratitis. The most consistent factor is overnight wear, which increases the risk for microbial keratitis by 10 to 15 times compared to daily wear, irrespective of lens type [9, 12, 50, 63–65]. The extended wear risk of infectious keratitis also increases by 9 times with aphakia correction in elderly patients; 12 times greater in patients misusing daily-wear lenses for overnight wear. Other risk factors include contact lens case hygiene, inadequate or lack of handwashing, infrequent case replacement, and smoking; wearing contact lenses while swimming or showering also increases the risk [27, 17, 66–71]. Contact lens wearers who live or travel to tropical locations also have a higher risk for microbial keratitis [18]. According to the lens type, the risk for microbial keratitis is as follows: daily disposable < rigid gas permeable < daily wear of soft contact lens < extended wear of soft contact lens [3, 35, 72].

Furthermore, contact lens wear results in a decrease in basal cell proliferation on the cornea and vertical migration of differentiated cells to the surface of the epithelium, and an abnormal accumulation of older epithelial cells [73, 74].

The pathogenesis of CLAIK is complex and involves intrinsic lens properties, including lens material and oxygen transmissibility and environmental variables such as bacterial contamination; user behavior, such as schedule wear and poor hygiene coupled with the alteration of normal corneal physiology, loss of epithelial adherence mechanisms and corneal erosions, lead to the development of microbial keratitis [12]. In summary, microbial contamination of the lens is followed by microbial adhesion to the corneal epithelium; then microtrauma or erosion to the epithelium occurs, resulting in the microbial invasion of the corneal stroma (**Figure 2**) [75].

### **7. Diagnosis**

Proper diagnosis of CLAIK is based on a complete ocular history of contact lens wear, patient's symptoms, a complete ophthalmological examination, corneal scrape, and culture, including the removed contact lens, the case, and solution [66].

#### **7.1 Symptoms and signs**

Symptoms common to microbial keratitis include a rapid onset of ocular pain, red eye, tearing, foreign body sensation, conjunctival mucopurulent discharge, and

#### **Figure 3.**

*53 years-old diabetic female using a one-month schedule silicone hydrogel disposable soft contact lenses in an overnight extended wear mode. The patient had been treated with 0.3% ciprofloxacin and prednisolone acetate 1% for one week. One day after stopping medications, a scrape and culture confirmed Staphylococcus spp. infection A. Left cornea showing three round dense stromal infiltrates with moderate stromal edema and Descemet folds. B. Positive fluorescein staining (>80% lesion surface) demarcating extensive corneal ulceration in all lesions. C. Three weeks on intense topical regime of 0.5% moxifloxacin and fortified vancomycin (50 mg/ ml), the ulcers resolved.*

photophobia with a variable degree of vision loss. These symptoms are be accompanied by prominent signs including, eyelid swelling, ciliary injection, conjunctival chemosis, a corneal epithelial defect or ulceration, stromal inflammatory/microbial infiltrate, edema, endothelial keratic precipitates (KPs), and anterior chamber reaction (inflammatory cells, flare, fibrin, plasmoid bodies, hypopyon) [11, 76–78].

There are clinical features that may guide the clinician to a possible etiological agent. Bacterial keratitis is characterized by a round, or oval epithelial defect with an underlying stromal infiltrate and anterior chamber reaction or hypopyon (**Figure 3A**–**C**) [66].

The classical findings in *Acanthamoeba* keratitis are severe pain that is disproportionate to the clinical signs, ring-shaped corneal infiltrates, and radial perineuritis [69, 75]. Fungal keratitis may present with a grayish, deep infiltrate with feathery borders and satellite lesions or an endothelial plaque and usually has a more insidious course [27, 66, 69]. However, these clinical findings are often misleading; in fact, cornea specialists distinguish correctly bacterial from fungal keratitis only 66% of the time in a photographic survey [79]. Thus, corneal scrapings and cultures remain the gold standard for microbial identification and the only method for determining antibiotic sensitivity [80].
