*4.1.1 Epidemiology*

Bacterial pathogens are responsible for a majority of infectious keratitis cases especially in developed countries and in contact lens wearers [21, 26, 27, 30, 43]. The keratitis can occur after a break in the corneal epithelium that allows bacteria to enter [43, 45]. The important pathogens of bacterial keratitis can be classified as follows: [18].

#### 1.Gram-positive bacteria


### 2.Gram-negative bacteria


The major bacterial causes are *Staphylococcus aureus*, *Coagulase-negative staphylococcus, Streptococcus pneumoniae Pseudomonas aeruginosa, and Streptococcus* spp. [18, 24, 66, 67].

#### *4.1.2 Manifestations*

The patient with bacterial keratitis usually presents with rapid onset of pain, photophobia, blurry vision, and eye redness. Slit lamp examination usually reveals

**11**

*Infectious Keratitis: The Great Enemy*

be suspected [17].

*4.1.3 Risk factors*

keratitis [18, 68].

*4.1.4 Treatment*

*DOI: http://dx.doi.org/10.5772/intechopen.89798*

clearly defined infiltrations with stromal edema and inflammation (**Figure 1**) [43, 45]. The classic clinical figures for Gram-positive cocci are "localized round or oval ulceration, grayish-white stromal infiltrates, distinct borders with minimal surrounding stromal haze, or no edema" [18, 24]. *Nontuberculous mycobacteria* usually have a "cracked wind-shield"-type of appearance. *Nocardia* spp. usually has a multiple small white infiltrate that resembles "wreath pattern." Gram negative bacterial infection usually presented as a dense stromal suppuration, hazy surrounding cornea, "immune ring" [18]. Pseudomonas keratitis may develop as ring abscess without epithelial defect [24]. Gram-negative bacterial keratitis can perforate within few days if not properly managed [24]. Keratitis caused by Gram-negative cocci usually present with lid edema and copious purulent discharge, perforate rapidly, and may have bilateral involvement [24]. However, the slit-lamp manifestation alone may not specify the definite pathogens. For instance, satellite lesions, immune ring, and endothelial plaques may be present in both bacterial and fungal keratitis and cannot help to differentiate between bacterial and fungal keratitis [24]. Appropriate microbiological investigation is needed to confirm the specific pathogens. Even among the cornea specialists, they can correctly differentiate culture-proven bacterial keratitis and smear-positive fungal keratitis in photographs in less than 70% of cases [55]. In the case that the keratitis is unresponsive to the initial treatment or has an atypical course, the mixed-organism infection such as bacterial combined with fungal keratitis should

The keratitis usually occurs after a break in the corneal epithelium [45, 68]. The major risk factors are contact lens wear, corneal abrasions, and ocular trauma [43, 45]. Other important risk factors include prior ocular surgery, chronic ocular disease, use of corticosteroids, contaminated ocular medications, and diabetes [66]. Contact lens wear and lagophthalmos were identified as the major risk factors for the development of Gram-negative infection [18, 66]. Preexisting ocular disease and previous HSV keratitis were associated with Gram-positive infectious

Topical antibiotic eye drops can achieve high tissue concentration and are the preferred method of treatment in most cases [69]. Topical fluoroquinolones usually prescribed as first-line empiric initial treatment of suspected bacterial keratitis are at least as effective as combined fortified antibiotics [69]. Even though the susceptibility of Gram-negative bacteria to fluoroquinolone monotherapy was high, the susceptibility of Gram-positive bacteria was less and more variable [11, 68]. Because of shift in antibiotics resistance patterns, in some regions, fluoroquinolone monotherapy is not recommended for severe infectious keratitis, but combined fortified antibiotics should be prescribed instead [11]. Fortified topical antibiotics should be considered for large and/ or visually significant keratitis, unresponsive to initial treatment, especially if a hypopyon is present [11, 44]. In contact lens wearers, the disease pattern and etiologic organisms may be altered to increase incidence of *Pseudomonas aeruginosa* [70]. Fluoroquinolones and aminoglycosides are good empirical antibiotics for infectious keratitis treatment [70]. In noncontact lens wearers, it tends to be caused by other organisms such as *coagulase-negative Staphylococci, Staphylococcus aureus*, *and Streptococcus pneumoniae*, which are largely sensitive

#### *Infectious Keratitis: The Great Enemy DOI: http://dx.doi.org/10.5772/intechopen.89798*

*Visual Impairment and Blindness - What We Know and What We Have to Know*

Bacterial pathogens are responsible for a majority of infectious keratitis cases especially in developed countries and in contact lens wearers [21, 26, 27, 30, 43]. The keratitis can occur after a break in the corneal epithelium that allows bacteria to enter [43, 45]. The important pathogens of bacterial keratitis can be classified as follows: [18].

*The classic clinical features of common causative organisms of infectious keratitis: (a) Bacterial keratitis. (b) Fungal keratitis. (c) Herpes necrotizing stromal keratitis. (d) Early Acanthamoeba keratitis. (e) Late* 

• Gram-positive cocci, e.g., *Staphylococcus aureus*, *Coagulase-negative staphylo-*

• Gram-positive bacilli, e.g., *Nontuberculous mycobacteria (Mycobacterium* 

• Gram-negative bacilli*; e.g., Pseudomonas aeruginosa, Enterobacteriaceae,* 

The major bacterial causes are *Staphylococcus aureus*, *Coagulase-negative staphylococcus, Streptococcus pneumoniae Pseudomonas aeruginosa, and Streptococcus*

The patient with bacterial keratitis usually presents with rapid onset of pain, photophobia, blurry vision, and eye redness. Slit lamp examination usually reveals

**10**

**4.1 Bacterial keratitis**

1.Gram-positive bacteria

2.Gram-negative bacteria

spp. [18, 24, 66, 67].

*4.1.2 Manifestations*

*Moraxella, Haemophilus*

*coccus, Streptococcus pneumoniae*

*fortuitum, Mycobacterium chelonae), Nocardia* spp*.*

• Gram-negative cocci; e.g., *Neisseria gonorrhea*

*4.1.1 Epidemiology*

*Acanthamoeba keratitis.*

**Figure 1.**

clearly defined infiltrations with stromal edema and inflammation (**Figure 1**) [43, 45]. The classic clinical figures for Gram-positive cocci are "localized round or oval ulceration, grayish-white stromal infiltrates, distinct borders with minimal surrounding stromal haze, or no edema" [18, 24]. *Nontuberculous mycobacteria* usually have a "cracked wind-shield"-type of appearance. *Nocardia* spp. usually has a multiple small white infiltrate that resembles "wreath pattern." Gram negative bacterial infection usually presented as a dense stromal suppuration, hazy surrounding cornea, "immune ring" [18]. Pseudomonas keratitis may develop as ring abscess without epithelial defect [24]. Gram-negative bacterial keratitis can perforate within few days if not properly managed [24]. Keratitis caused by Gram-negative cocci usually present with lid edema and copious purulent discharge, perforate rapidly, and may have bilateral involvement [24]. However, the slit-lamp manifestation alone may not specify the definite pathogens. For instance, satellite lesions, immune ring, and endothelial plaques may be present in both bacterial and fungal keratitis and cannot help to differentiate between bacterial and fungal keratitis [24]. Appropriate microbiological investigation is needed to confirm the specific pathogens. Even among the cornea specialists, they can correctly differentiate culture-proven bacterial keratitis and smear-positive fungal keratitis in photographs in less than 70% of cases [55]. In the case that the keratitis is unresponsive to the initial treatment or has an atypical course, the mixed-organism infection such as bacterial combined with fungal keratitis should be suspected [17].

#### *4.1.3 Risk factors*

The keratitis usually occurs after a break in the corneal epithelium [45, 68]. The major risk factors are contact lens wear, corneal abrasions, and ocular trauma [43, 45]. Other important risk factors include prior ocular surgery, chronic ocular disease, use of corticosteroids, contaminated ocular medications, and diabetes [66]. Contact lens wear and lagophthalmos were identified as the major risk factors for the development of Gram-negative infection [18, 66]. Preexisting ocular disease and previous HSV keratitis were associated with Gram-positive infectious keratitis [18, 68].

## *4.1.4 Treatment*

Topical antibiotic eye drops can achieve high tissue concentration and are the preferred method of treatment in most cases [69]. Topical fluoroquinolones usually prescribed as first-line empiric initial treatment of suspected bacterial keratitis are at least as effective as combined fortified antibiotics [69]. Even though the susceptibility of Gram-negative bacteria to fluoroquinolone monotherapy was high, the susceptibility of Gram-positive bacteria was less and more variable [11, 68]. Because of shift in antibiotics resistance patterns, in some regions, fluoroquinolone monotherapy is not recommended for severe infectious keratitis, but combined fortified antibiotics should be prescribed instead [11]. Fortified topical antibiotics should be considered for large and/ or visually significant keratitis, unresponsive to initial treatment, especially if a hypopyon is present [11, 44]. In contact lens wearers, the disease pattern and etiologic organisms may be altered to increase incidence of *Pseudomonas aeruginosa* [70]. Fluoroquinolones and aminoglycosides are good empirical antibiotics for infectious keratitis treatment [70]. In noncontact lens wearers, it tends to be caused by other organisms such as *coagulase-negative Staphylococci, Staphylococcus aureus*, *and Streptococcus pneumoniae*, which are largely sensitive

to fluoroquinolones [70]. In terms of patients' tolerance to medications, fluoroquinolones are more favorable than combined fortified antibiotics [69]. The initial empirical therapy should be prescribed until definite microbial identity and sensitivity are disclosed [11]. For central or severe keratitis, a loading dose every 5–15 minutes followed by frequent applications such as every hour is recommended [24, 44]. Subconjunctival antibiotics may be useful in impending scleral spreading and questionable adherence to topical treatment. In cases of scleral or intraocular extension of infection, perforation, or systemic infection, systemic therapy may be helpful [24, 44]. Oral tetracycline class antibiotics (including doxycycline) could be used to inhibit corneal stromal thinning by matrix metalloproteinases [71].

Reevaluation depends on the extent and severity of disease. The initial treatment should be modified when the eye shows a lack of improvement or stabilization within 48 hours [44]. Coexisting conditions and/or complications, such as glaucoma, corneal perforation, endophthalmitis, and eye lid abnormalities, should be treated promptly. The progressive corneal stromal thinning should be managed by application of tissue adhesive, penetrating keratoplasty, or lamellar keratoplasty [44]. Therapeutic keratoplasty may be indicated in cases of large corneal perforation or uncontrolled infection [24, 44]. Corneal transplantation in active infection has high failure rate [34]. However, the result is usually better than fungal keratitis, and 40–50% of these patients recover useful vision [24].

#### **4.2 Fungal keratitis**

## *4.2.1 Epidemiology*

Fungal keratitis, potentially blinding condition, is an important cause of infectious keratitis [72]. Fungal keratitis is very common, accounts for 30–62% of infectious keratitis, in tropical region, but is uncommon in temperate climates [72]. The important pathogens of fungal keratitis can be classified as follows [18, 24, 45, 61, 72]:

Filamentous fungi such as *Aspergillus* spp., *Fusarium* spp., *Curvularia* spp., and *Scedosporium* spp. are frequent causes.

Yeasts such as *Candida albicans*, *Candida* spp., and *Cryptococcus* spp., are less common [18]. The fungi invade the ocular surface only when it is compromised or has a defect in the epithelial barrier and access into the corneal stroma [72]. However, the keratitis may present as chronic infiltration or even with an intact epithelium [56].

#### *4.2.2 Manifestations*

Symptoms of fungal keratitis typically are not as acute as other microbial keratitis [72]. The pain, redness, and lid edema are similar with bacterial keratitis. Early fungal keratitis may appear like a dendritic ulcer of herpes simplex virus. The feathery edge is a pathognomonic clinical feature [24]. Satellite lesions, immune ring, and unlevelled hypopyon may support the diagnosis but not specific clinical figures [24]. The surface is raised with grayish-white creamy infiltrates, which may or may not appear dry [24]. The keratitis due to pigmented fungi such as Curvularia spp., Bipolaris, and Exserohilum spp. will appear as brown or dark, raised, dry, rough, leathery plaque on the corneal surface [24, 46]. A recent report from the Mycotic Ulcer Treatment Trial II (MUTT II) stated that the presence of hypopyon at baseline indicated 2.28 times the odds of the patient developing corneal perforation and/or needing therapeutic keratoplasty [73].

**13**

*Infectious Keratitis: The Great Enemy*

*4.2.3 Risk factors*

*4.2.4 Treatment*

*DOI: http://dx.doi.org/10.5772/intechopen.89798*

Fungal keratitis must be suspected if the patient is in agricultural work [24]. For filamentous fungi, trauma with subsequent exposure to plant or vegetable material is usually the only predisposing factor, although previous use of corticosteroids, native medicine, and contact lens wear are increasing in importance as risk factors [24, 45, 61].

The currently available antifungal drugs have multiple drawbacks such as poor ocular penetration, unpredictable bioavailability, and adverse effects associated with systemic medications [47]. Filamentous fungal keratitis is difficult to treat despite the use of topical and systemic antifungal agents and adjuvant surgery, such as corneal transplantation [61]. About one-third of fungal keratitis patients have pharmacological failure that required surgical interventions to get rid of infection [72]. Thus, early diagnosis of fungal keratitis is the most important determinant of their prognosis [56]. Topical corticosteroids are contraindicated in the treatment of fungal keratitis and also in the early postoperative therapeutic keratoplasty [72]. For filamentous fungi, the first-line drug is 5% natamycin, and the second-line drugs are 1% itraconazole and 2% Econazole [18]. There is evidence that natamycin is more effective than voriconazole in the treatment of filamentous fungal keratitis especially in Fusarium keratitis [74, 75]. *Candida keratitis* is usually initially treated with 0.15% amphotericin B followed by fluconazole eye drop if the first-line drug is not responsive [18]. The systemic antifungal agents, including oral ketoconazole, itraconazole, voriconazole, and posaconazole, are needed for severe keratitis or cases with extension beyond the anterior chamber [18, 43]. Seventy percent of Fusarium keratitis with deep lesion does not respond to sole medical treatment, and surgical intervention may be required [61]. More than 80% of Aspergillus keratitis responds to medical therapy alone; however, in deep keratitis, surgical intervention is needed [61]. For Candida keratitis, medical therapy generally has a favorable response, and the presence of deep lesions is not a major issue [61]. Severe fungal keratitis patients that are still smear-positive despite being pretreated with appropriate antifungal agents may benefit from aggressive multimodality therapy [76]. Various drugs and route of antifungal agents for

For yeast, there is usually some systemic or ocular surface compromise [61].

fungal keratitis are available as listed below [9, 18, 47, 60, 61, 75, 77–79].

nazole (50–200 mg/day), and voriconazole (400 mg/day)

(10 mg in 0.5 mL), and voriconazole (10 mg)

conazole (6 mg/kg)

(5–10 μg per 0.1 mL)

1.Topical: natamycin (5%), amphotericin B (0.15–0.3%), Econazole (1%), Flucytosine (1%), clotrimazole (1%), miconazole (1%), ketoconazole (1–2%), itraconazole (1%), fluconazole (1%), voriconazole (1–2%), and caspofungin (0.5%)

2.Subconjunctiva: fluconazole (0.5–1.0 mL of a 2% solution), miconazole

3.Intravenous: amphotericin B and miconazole (600–1200 mg/day), and vori-

4.Oral: ketoconazole (200–600 mg/day), itraconazole (100–200 mg/day), fluco-

5.Intrastromal injection: voriconazole (50 μg per 0.1 mL) and amphotericin B

6.Intracameral: voriconazole (50 μg /0.1 mL) and amphotericin B (5–10 μg/0.1 mL)
