Publication Exclusive: Corneal cross-linking may have application in infective keratitis

Corneal cross-linking has been popularly used to prevent progression of keratoconus and corneal ectasia. The procedure is based on using riboflavin as a photosensitizer, which generates reactive oxygen species when activated by ultraviolet A at 365 nm. It induces a photochemical reaction that forms covalent bonds or cross-links in the corneal stroma. In the last decade, it has been introduced in keratitis and infective corneal ulcers that are resistant to drugs. With the rising incidence of multidrug resistance, corneal infections are increasing and devastating consequences are faced in aggressive microbial infections. Corneal cross-linking has provided a significant contribution in controlling the pathogenesis of the infections.

History

In 1965, Tsugita and colleagues noted that riboflavin, when subjected to either visible or UV light, could inactivate the RNA of tobacco mosaic virus. Spoerl and colleagues proved by in vitro study that a cross-linked cornea is more resistant to collagenases enzymatic activity than the normal or diseased cornea. Although there have been studies showing the antibacterial activity of riboflavin with UV light in vitro, the pilot study on human eyes was performed by Makdoumi and colleagues. They performed a pilot study to investigate the photochemical interaction used in corneal cross-linking as the primary therapy for bacterial keratitis. For microbial keratitis, Hafezi and colleagues named the therapy photoactivated chromophore for keratitis corneal cross-linking, or PACK-CXL.

Amar Agarwal

Role of cross-linking in infection

Microbes are known to develop resistance to drugs due to chromosomal mutation or exchange of genetic material by transformation, conjugation or bacteriophage transduction. As drug-resistant infections peak day by day, newer modalities of treatment are inevitable. UV light-based corneal cross-linking with riboflavin can function in the following ways:

1. Riboflavin interacts with the DNA of the microbes and inhibits replication. Riboflavin has a planar ring that intercalates between bases of DNA and RNA, which results in the oxidation of nucleic acids on exposure to UV light.

2. Oxidative damage to pathogens is also mediated by nonspecific photochemical reactions. Injury or damage to the microbial cell wall releases active free oxygen species.

3. Ultraviolet irradiation itself has a dose-dependent ability to directly destroy micro-organisms. This property has been used in sterilization processes.

Bacterial infections: Cross-linking also induced structural changes in the stromal collagen, which prevents the further cleavage action of collagenases. In vitro studies have demonstrated its bactericidal effect against Staphylococcus aureus, S epidermidis, Pseudomonas aeruginosa, Streptococcus pneumoniae and MRSA.

Fungal infections: Corneal cross-linking does not eradicate Candida albicans, Fusarium species or Aspergillus fumigatus in vitro, although it may enhance the effect of antifungal medications.

Acanthamoeba infections: Acanthamoeba species are also difficult to eradicate due to their prolonged and aggressive nature and structural difference. However, healing can be enhanced and the effect of enzymatic digestion on the cornea can be prevented after cross-linking.

Click here to read the full publication exclusive, Complications Consult, published in Ocular Surgery News U.S. Edition, August 10, 2015.