**8. Recent treatments of infectious keratitis**

The mainstay treatment of infectious keratitis is antimicrobial drugs, which is fraught with drug resistance [11]. However, despite appropriate diagnosis and urgent treatment, medical treatment failure may occur and lead to corneal perforation [101] and/or therapeutic keratoplasty. Novel treatment is emerging to expand the armamentarium of tools to manage infectious keratitis and improve treatment outcomes [101]. The interesting managements in recent years are Photo-Activated Chromophore for Keratitis–Corneal Cross-Linking (PACK-CXL) and photodynamic antimicrobial therapy (PDAT) [91, 101–103].

#### **8.1 PACK-CXL**

The mechanism of action of PACK-CXL is antimicrobial activity of UV light, which can directly damage the DNA and RNA of various etiologic organisms [91]. Moreover, synergistic effect is derived from reactive oxygen species released from photoactivated riboflavin, which can directly damage DNA and cell membranes of microorganisms [91]. These effects can increase corneal resistance to enzymatic

**19**

**9. Conclusion**

**Conflict of interest**

*Infectious Keratitis: The Great Enemy*

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

**8.2 Photodynamic antimicrobial therapy (PDAT)**

and fungal keratitis with good long-term outcome [112].

lens care and hygiene must be strongly emphasized.

The authors declare no conflict of interest.

degradation and increase corneal rigidity. So, it may decrease corneal melting and avoid emergency therapeutic keratoplasty [102, 104]. As microbial resistance to microbicidal therapy increases, CXL might be effective in treating advanced infectious keratitis as an adjuvant and also for treating early-stage bacterial infiltrates as first-line treatment [102, 104]. However, CXL is not routinely used for infectious keratitis because of the uncertainty of its safety and efficacy. A recent systematic review and meta-analysis from Ting et al. demonstrated that adjuvant PACK-CXL could expedite the resolution of bacterial keratitis and potentially fungal keratitis, in terms of size of infiltrates [105, 106]. However, adjuvant PACK-CXL did not shorten the time to corneal healing [107]. Unfortunately, in Acanthamoeba, viral, fungal, and mixed keratitis, treatment outcome was insufficient [91, 103]. However, when rose Bengal was used instead of riboflavin, PACK-CXL was effective against Acanthamoeba [108]. UV radiation in PACK-CXL may exacerbate viral keratitis [109].

Since CXL was found to be ineffective against fungal keratitis, potential blinding disease, PDT was proposed as an alternative measure [103]. Photodynamic therapy (PDT) involves the activation of a photosensitizing agent that reacts with oxygen to create reactive oxygen species (ROS). The light using in PDT ranges from ultraviolet-A (UV-A) to near-infrared wavelengths. These ROS react with intracellular components and produce cell inactivation and death [110]. In vitro study demonstrated that Rose Bengal-mediated PDT successfully inhibited the growth of *Fusarium solani, Aspergillus fumigatus*, and *Candida albicans* [103]. Moreover, the Rose Bengal- and riboflavin-mediated PDT demonstrated in vitro inhibition of methicillin-resistant *Staphylococcus aureus* (MRSA) [111]. Riboflavin PDAT strengthens the corneal collagen fibers, delays keratolysis, and prevents a corneal perforation in humans [112]. This can be used as an adjunct treatment in bacterial

Infectious keratitis tops the list of the diseases leading to visual impairment and corneal blindness. The precise clinical diagnosis, accurate diagnostic tools, and timely appropriate management are important to reduce the morbidity associated with infectious keratitis. Although most patients improve after medical and surgical management, their vision may be considerably decreased [15]. A few emerging treatments used to manage infectious keratitis show good preliminary outcomes for selected cases of infectious keratitis, although additional research is required before it is accepted as mainstream treatment for this potentially blinding condition. Therefore, the importance of eye protection [18], hygiene education, and contact

*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*

penetrating keratoplasty than voriconazole-treated cases [74].

Nocardia keratitis [96, 97].

**7.2 Mycotic Ulcer Treatment Trial (MUTT) I**

**7.3 Mycotic Ulcer Treatment Trial (MUTT) II**

**7.4 The Herpetic Eye Disease Study (HEDS) I**

**7.5 The Herpetic Eye Disease Study (HEDS) II**

HSV keratitis by 50% approximately [88, 100].

**8. Recent treatments of infectious keratitis**

namic antimicrobial therapy (PDAT) [91, 101–103].

not caused by Nocardia species. But no significant difference was identified by treatment for scar size for non-Nocardia ulcers. However, scar size was larger in

The double-masked, multicenter trial that compare topical 5% natamycin vs. 1% voriconazole in the treatment of filamentous fungal keratitis showed a benefit of topical natamycin over topical voriconazole for filamentous fungal keratitis, particularly among those caused by Fusarium. Natamycin-treated cases had significantly better 3-month BSCVA, less likely to have perforation or require therapeutic

The randomized, placebo-controlled, double-masked multicenter clinical trial showed that adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal keratitis did not improve the rate of corneal perforation, the need for therapeutic penetrating keratoplasty (TPK), microbiologic cure at 6 days, rate of re-epithelialization, BSCVA, and infiltrate and/or scar size. However,

The Herpetic Eye Disease Study (HEDS) was a series of randomized, doublemasked, placebo-controlled clinical trials that studied ocular HSV and is still the gold standard for ocular HSV management [86]. HEDS showed a significant benefit of topical corticosteroids and oral acyclovir for HSV stromal keratitis [84, 99].

HEDS II showed that oral acyclovir decreased the recurrence rate of any type of

The mainstay treatment of infectious keratitis is antimicrobial drugs, which is fraught with drug resistance [11]. However, despite appropriate diagnosis and urgent treatment, medical treatment failure may occur and lead to corneal perforation [101] and/or therapeutic keratoplasty. Novel treatment is emerging to expand the armamentarium of tools to manage infectious keratitis and improve treatment outcomes [101]. The interesting managements in recent years are Photo-Activated Chromophore for Keratitis–Corneal Cross-Linking (PACK-CXL) and photody-

The mechanism of action of PACK-CXL is antimicrobial activity of UV light, which can directly damage the DNA and RNA of various etiologic organisms [91]. Moreover, synergistic effect is derived from reactive oxygen species released from photoactivated riboflavin, which can directly damage DNA and cell membranes of microorganisms [91]. These effects can increase corneal resistance to enzymatic

oral voriconazole did increase in nonserious adverse events and cost [98].

**18**

**8.1 PACK-CXL**

degradation and increase corneal rigidity. So, it may decrease corneal melting and avoid emergency therapeutic keratoplasty [102, 104]. As microbial resistance to microbicidal therapy increases, CXL might be effective in treating advanced infectious keratitis as an adjuvant and also for treating early-stage bacterial infiltrates as first-line treatment [102, 104]. However, CXL is not routinely used for infectious keratitis because of the uncertainty of its safety and efficacy. A recent systematic review and meta-analysis from Ting et al. demonstrated that adjuvant PACK-CXL could expedite the resolution of bacterial keratitis and potentially fungal keratitis, in terms of size of infiltrates [105, 106]. However, adjuvant PACK-CXL did not shorten the time to corneal healing [107]. Unfortunately, in Acanthamoeba, viral, fungal, and mixed keratitis, treatment outcome was insufficient [91, 103]. However, when rose Bengal was used instead of riboflavin, PACK-CXL was effective against Acanthamoeba [108]. UV radiation in PACK-CXL may exacerbate viral keratitis [109].

#### **8.2 Photodynamic antimicrobial therapy (PDAT)**

Since CXL was found to be ineffective against fungal keratitis, potential blinding disease, PDT was proposed as an alternative measure [103]. Photodynamic therapy (PDT) involves the activation of a photosensitizing agent that reacts with oxygen to create reactive oxygen species (ROS). The light using in PDT ranges from ultraviolet-A (UV-A) to near-infrared wavelengths. These ROS react with intracellular components and produce cell inactivation and death [110]. In vitro study demonstrated that Rose Bengal-mediated PDT successfully inhibited the growth of *Fusarium solani, Aspergillus fumigatus*, and *Candida albicans* [103]. Moreover, the Rose Bengal- and riboflavin-mediated PDT demonstrated in vitro inhibition of methicillin-resistant *Staphylococcus aureus* (MRSA) [111]. Riboflavin PDAT strengthens the corneal collagen fibers, delays keratolysis, and prevents a corneal perforation in humans [112]. This can be used as an adjunct treatment in bacterial and fungal keratitis with good long-term outcome [112].

### **9. Conclusion**

Infectious keratitis tops the list of the diseases leading to visual impairment and corneal blindness. The precise clinical diagnosis, accurate diagnostic tools, and timely appropriate management are important to reduce the morbidity associated with infectious keratitis. Although most patients improve after medical and surgical management, their vision may be considerably decreased [15]. A few emerging treatments used to manage infectious keratitis show good preliminary outcomes for selected cases of infectious keratitis, although additional research is required before it is accepted as mainstream treatment for this potentially blinding condition. Therefore, the importance of eye protection [18], hygiene education, and contact lens care and hygiene must be strongly emphasized.

### **Conflict of interest**

The authors declare no conflict of interest.
