**8. Differential diagnosis**

#### **8.1 Microorganism profile**

According to the clinical features of the infectious/inflammatory process seen in CLAIK, specific differences, although not compelling, help identify the infectious agent involved in the process. For example, Gram-negative bacteria are usually associated with a significant anterior chamber reaction and larger ulcers compared to Gram-positive ones. Also, *Pseudomonas aeruginosa* tends to produce larger stromal inflammatory infiltrates [2, 40]. A study analyzing the causative microorganism involved in CLAIK found moderate positive prediction for *Acanthamoeba* annular

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

#### **Figure 6.**

*A. Sterile peripheral inflammatory infiltrate in the right eye due to corneal hypoxia and a tight lens fitting of a 26-year-old female wearing hydrogel-silicone, one-month schedule disposable contact lenses complaining of redeye, foreign body sensation, and tearing from the past three days. B. Fluorescein staining shows a slight epithelial defect at the infiltrated site and superficial punctate keratitis.*

stromal infiltrate at 89% (95% CI = 52–100) and *Pseudomonas* larger ulcer at 65% (95% CI = 43–84) [114]. On the other hand, pseudo-dendrites, epitheliopathy, and stromal infiltrate found in *Acanthamoeba* keratitis may confuse herpetic keratitis [115]. Serrated (feathery) ulcer margins with raised and dry texture infiltrate and satellite lesions are common features of fungal keratitis [116].

#### **8.2 Infectious versus inflammatory keratitis**

One of the first dilemmas confronted by professionals taking care of patients wearing contact lenses is to know if the corneal lesion is infectious or inflammatory (**Figure 6A** and **B**). The difficulty arises because the ocular immune response to foreign stimuli, including microbes and their products, foreign bodies, trauma, allergic and toxic reactions, is non-specific inflammation, which may be indistinguishable from infection in that respect [78, 117, 118]. A study asking ophthalmologists to identify sterile from culture-proven CLAIK found good predictability (76%, 95% CI = 67–84) with 79 cases classified correctly [114].

Some key clinical features help to differentiate between sterile from infectious keratitis. In sterile inflammation, the absence of eyelid edema, no conjunctival discharge, peripheral location of the lesion, and minimal or no anterior chamber reaction contrast with significant eyelid edema, abundant mucopurulent discharge, central/paracentral lesions, and severe reaction and hypopyon formation in infectious keratitis [78].

### **9. Management**

First and foremost, efforts should be focused on the prevention of CLAIK. Wearers should be educated on the proper use of contact lenses. They should be counseled to avoid overnight wear and exposure to water and be educated on appropriate hygiene practices when handling contact lenses and timely contact lens replacement [35].

To make the right management decisions, recognizing the risk factors for CLAIK, its different clinical infectious patterns, and getting the causal microorganism identification/isolation are critical to obtaining an optimal therapeutic response, avoiding sight-threatening severe complications.

### **9.1 Bacterial keratitis**

An early diagnosis and appropriate treatment of infectious keratitis are essential. Broad-spectrum topical antibiotics are the first-line therapy for bacterial keratitis and should be initiated immediately after cultures are obtained, while waiting for the results. Antibiotics should be indicated, taking into consideration the local epidemiological data, frequency of specific pathogens, and antibiotic sensitivities (**Table 5**) [82, 119]. Severe keratitis should be treated with an initial loading dose every 5 to 15 minutes for the first hour, followed by hourly instillation for 24 to 48 hours; a topical fortified antibiotic or fluoroquinolone may be used [119].

In a recent meta-analysis, no difference in effectiveness, defined as complete corneal re-epithelialization, was observed between the use of commercially available fourth-generation topical fluoroquinolones and aminoglycoside-cephalosporin fortified combinations; there was no difference in time to resolution either. However, symptoms of ocular discomfort and toxic conjunctivitis were more frequent when using fortified aminoglycoside-cephalosporin combinations (see Appendix 1) [119].

Treatment should be tapered according to response to a minimum of four times a day, avoiding toxicity from prolonged and unnecessary use of antibiotics [112]. If no clinical stabilization or improvement is observed after the first 48 hours of treatment, the therapeutic regimen should be modified; culture results and antibiotic sensitivity should guide the clinician under these conditions. Good therapeutic response features include decreased pain, conjunctival discharge, eyelid edema, reduced corneal stromal edema, a decreased anterior chamber response, and signs of re-epithelialization. Patients with severe keratitis should be followed daily until clinical improvement is observed. Cycloplegic agents may be indicated in cases of severe keratitis with significant anterior chamber reaction to prevent the formation of irissynechiae and reduce the pain [63].

The use of topical corticosteroids is controversial but may have a role in treating certain bacterial keratitis to reduce corneal scarring. According to a subgroup analysis of the Steroids for Corneal Ulcers Trial (SCUT) in non-*Nocardia* bacterial keratitis, topical corticosteroids within two to three days of topical antibiotic therapy resulted in a one-line improvement in visual acuity compared to placebo [120]. However, topical corticosteroid use in *Nocardia* ulcers was associated with larger scars at 12 months, and therefore, it is not recommended for these cases [121]. Other well-designed randomized clinical trials are necessary to confirm these findings [122] .

#### **9.2 Fungal keratitis**

Fungal keratitis is often more aggressive than bacterial keratitis. However, there is no consensus on standard treatment, and randomized clinical trials on this subject are scarce [122]. Most antifungal medications available for ocular infections have significant limitations, including low bioavailability and limited ocular penetration in deep-seated lesions (**Table 6**) [123–125]. Furthermore, antifungal susceptibility testing has limited availability and is rarely used in ordinary contact lens and cornea clinics [126]. The Mycotic Ulcer Treatment Trial I (MUTT I) showed that topical natamycin is superior to topical voriconazole treating fungal keratitis in general, particularly in those caused by *Fusarium* [127]. According to the MUTT II results, there is no difference in perforation rate or need for therapeutic penetrating keratoplasty in fungal ulcers treated with oral voriconazole combined with topical antifungal agents compared to oral placebo and equal antifungal topical therapy. However, systemic adverse events were more frequent in the oral voriconazole group


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

*Adapted and modified from Mannis MJ and Holland EJ (Eds.). (2017). Cornea. Elsevier.*

*NTM, non-tuberculous mycobacteria; TMP-SMX, trimethoprim-sulfamethoxazole.<sup>1</sup> Also used when no organism or multiple types or organisms are identified.*

*2 Systemic therapy is required for suspected gonococcal infection.*

*3 Potent activity against methicillin-resistant Staphylococcus aureus; used for resistant Enterococcus species and penicillin allergy. Must not be used as single therapy against bacterial keratitis due to poor gram-negative activity. 4 Mostly used in ointment presentation for the management of blepharitis, rarely used in keratitis due to poor corneal penetration.*

*5 Active against gram-negative and -positive bacteria; however, used because bacteria become highly resistant during therapy.*

*6 Rarely used in bacterial keratitis due to poor corneal penetration when intact epithelium.*

#### **Table 5.**

*Topical and subconjunctival antibiotics and their indication for microbial keratitis.*


#### **Table 6.**

*Topical antifungals formulations for the treatment of mycotic keratitis.*

[128]. According to a metanalysis of the available randomized clinical trials, there is still limited evidence to support using any particular drug or combination of drugs to treat fungal keratitis [129]. In general, topical treatment may include natamycin 5%, amphotericin-B 0.15% to 0.5 %, or voriconazole 1% or 2% [122].
