Abstract

Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed.

Highlights

  • According to the World Health Organization (WHO), around 6 million people globally are affected by cornea-related blindness [1]

  • We focus on the advancement of antimicrobial PDT (aPDT) against fungal keratitis, to spotlight a less studied area and enhance the awareness of this area of translational studies

  • PSs used in aPDT for infectious keratitis (IK) include toluidine blue O (TBO), methylene blue (MB) [74,75], rose bengal (RB) [20], and riboflavin (RBF) [76,77]

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Summary

Introduction

According to the World Health Organization (WHO), around 6 million people globally are affected by cornea-related blindness [1]. The situation is complicated by the rapid emergence of drug-resistant fungal keratitis globally [5,6], to the extent that some patients require a full thickness corneal transplantation (penetrating keratoplasty) [7] as treatment. In their 1991 study, Kirkness et al suggested early intervention with corneal transplantation regarding the management of advanced microbial keratitis [8]. New and novel therapies are crucially required to treat and prevent drug-resistant fungal infections. We focus on the advancement of aPDT against fungal keratitis, to spotlight a less studied area and enhance the awareness of this area of translational studies

Fungal Keratitis
Drug Resistance and Biofilm in Fungal Keratitis
The History of Antimicrobial Photodynamic Therapy
Mechanism of the Photodynamic Action in Fungal Infection
Antimycotic Photodynamic Therapy
First-Generation Photosensitizers
Second-Generation Photosensitizers
Phenothiaziniums
Phthalocyanines
Riboflavin
Schematic
Rose Bengal
Challenges in Trans-Corneal Drug Delivery
Findings
10. Conclusions
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