Challenges of corneal infections

Abstract

Introduction Ocular infections remain an important cause of blindness worldwide and represent a challenging public health concern. In this regard, microbial keratitis due to fungal, bacterial, or viral infection can result in significant vision loss secondary to corneal scarring or surface irregularity. Left untreated corneal perforation and endophthalmitis can result, leading to loss of the eye. Rigorously studied animal models of disease pathogenesis have provided novel information that suggests new modes of treatment that may be efficacious clinically and emerging clinical data is supportive of some of these discoveries. Areas covered This review focuses on advances in our understanding of disease pathogenesis in animal models and clinical studies and how these relate to improved clinical treatment. We also discuss a novel approach to treatment of microbial keratitis due to infection with these bacterial pathogens using PACK-CXL and recommend increased basic and clinical studies to address and refine the efficacy of this procedure. Expert commentary Because resistance to antibiotics has developed over time to these bacterial pathogens, caution must be exercised in treatment. Attractive novel modes of treatment that hold new promise for further investigation include lipid based therapy, as well as use of small molecules that bind deleterious specific host responsive molecules and use of microRNA based therapies.

A Review of the Cytokine IL-17 in Ocular Surface and Corneal Disease

“…(31) The most common risk factors for bacterial keratitis include ocular trauma, surgery, concurrent ocular surface disease, immunosuppression and the use of contact lenses. (7,32) Similar to other bacterial infections, the pathogenesis of bacterial keratitis (caused primarily by extracellular bacteria) is dependent on the species of the bacteria, the virulence factors and host immune response. (33) Heimer et al (Table 1) investigated the gene expression of human corneal epithelial cells secondary to infection with Staphylococcus aureus.…”

“…(38,39) Infiltration of innate immune cells and upregulation of pro-inflammatory, chemotactic, and regulatory cytokines is the vigorous immune response that patients with keratitis mount to Aspergillus and Fusarium hyphae formation. (7) Studies have shown that individuals with a compromised IL-17 response, primarily as a results of autoantibodies against IL-17, are more vulnerable to yeast fungal infections, particularly candidiasis at mucosal surfaces. (40,41) Other studies have shown that mutations in the STAT3 gene, which is required for the production of IL-17, increase the susceptibility of individuals to infections with Candida.…”

“…An understanding of this relationship, and who this then effects is crucial, as the biochemical pathways would allow for the development of novel modes of treatment that may be efficacious clinically, however more studies are needed in this area, particularly human studies. (7) F o r P e e r R e v i e w O n l y 3 Of interest in this discussion is interleukin (IL)-17 (IL-17) and its role in ocular surface disease and infective keratitis. The major cellular component of corneal lesions, at all of the phases of keratitis pathogenesis, are derived primarily from neutrophils that induce inflammatory events that lead to tissue damage ( Figure 1).…”

Ocular Glands Become Infected Secondarily to Infectious Keratitis and Play a Role in Corneal Resistance to Infection

“…6D) at 5 days p.i. Next, we used a 32-plex bead-based protein assay to determine whether the expression of inflammatory mediators both known and unknown to ocular HSV-1 had altered expression in this model (16). Surprisingly, no change was found in analyte expression between the corneas of mice with and without HGs at 5 days p.i.…”

“…In 2010, the Centers for Disease Control and Prevention reported that 700,000 clinical visits occurred due to microbial infections of the cornea, or microbial keratitis, in the United States (14). Depending on the pathogen, tissue pathology can occur by direct cytopathic effects (e.g., virus), secreted toxins (e.g., bacteria), or immunemediated damage that can result in opacity and scar formation of the cornea (15,16). Host clearance of the insulting pathogen can also lead to corneal neovascularization (comprised of blood and lymphatic vessel formation), as in cases of herpes simplex virus 1 (HSV-1) keratitis (15).…”