WRITER Dr Sanjay Marasini

Promising new treatments for microbial keratitis (MK) are on the horizon with New Zealand research showing low-intensity ultraviolet-C light (UVC) may manage the potentially sightthreatening infection safely and effectively.

In preclinical trials, a 15-second exposure to UVC, administered twice daily, has been shown to effectively manage severe bacterial corneal infections within two days.

Microbial keratitis (an infective corneal ulcer) is a severe infection of the cornea caused by various microorganisms, including bacteria, fungi, viruses, and acanthamoeba.1 Predisposing factors are well-defined and include ocular trauma, contact lens use, eye surgeries, ocular surface diseases, compromised immune systems, and diabetes.1

Each year, approximately two million people are affected by MK worldwide, and the condition is considered an epidemic in some parts of the world, particularly within South, Southeast, and East Asia.2 In Australia, the median cost of care for all types of MK was AU$8,013 for the cases managed between 2015 and 2020 and the total cost of MK is estimated to be $13.58 million per year.3 In MK, the largest component of costs of care are hospital visits and hospital bed days.1

SUBOPTIMAL OUTCOMES

Accurate identification of the infecting microorganism in MK – whether bacterial, fungal, viral, or acanthamoeba – is essential for effective treatment. This is typically achieved through corneal debridement from the site of infection and laboratory culture of the specimen collected. Currently, an empiric therapy is then initiated to manage the infection in the interim. Empiric therapy involves the frequent application of broad-spectrum antibiotic eye drops every 30 to 60 minutes, to inhibit the growth of a range of microorganisms.

The treatment is generally selected based on the ulcer’s appearance, the patient’s history, and associated clinical characteristics – an experienced clinician may be able to detect the type of an infection by considering these factors. Once laboratory results are available, the treatment is tailored to target the specific pathogens. However, the wait time of 24–48 hours for laboratory reports, combined with antibiotic resistance, often results in suboptimal treatment outcomes. Also, clinical signs of MK can overlap and complicate diagnosis, sometimes leading to inappropriate treatments, such as steroids, which can worsen the infection.

The rise of antibiotic resistance, coupled with the lack of new antibiotic classes, underscores the urgent need to explore novel infection management strategies. Non-antibiotic approaches are now a high-priority research area.

A NOVEL APPROACH

The Ocular Surface Laboratory in the University of Auckland is investigating the use of non-pharmacological methods to manage corneal infections, such as light-based antiinfective technology.

Our laboratory has shown that low-intensity ultraviolet-C light (UVC, 265 nm, 1.93 mW/cm²) has a potential to manage MK safely and effectively.

UVC is effectively absorbed by microbial DNA, causing photochemical reactions that impair DNA functions and inhibit microbial growth. Due to their simpler cellular structures, microorganisms require significantly lower doses of UVC – about 20 times less – than what is needed to affect human corneal cells.

UVC can kill most bacteria, yeast, fungi, and other pathogens, regardless of their antibiotic resistance profiles. For instance, methicillinresistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, which are increasingly associated with MK, show high susceptibility to UVC.

In preclinical studies, our laboratory simulated different types of corneal infections, including those caused by antibiotic resistant bacterial strains (e.g., MRSA, Haemophilus influenzae, Streptococcus pneumoniae), yeast (Candida albicans) and fungi (Aspergillus species), and tested the therapeutic efficacy of UVC.4,5

We determined that a single 15-second exposure to UVC, administered twice daily, can effectively manage severe bacterial corneal infections within two days.

Since UVC can kill all types of microorganisms, as well as those growing together in a polymicrobial infection, which is a common feature of MK, it has the potential to be an empiric treatment. This suggests that adjunctive antibiotic treatments may not always be necessary to prevent secondary infections. The therapeutic doses of UVC seem to be promising in terms of safety to the cornea assessed in terms of DNA damage,5 depth of penetration through the cornea,5 and the impact on limbal stem cells.6

Unlike corneal collagen cross-linking, which uses UVA light in combination with riboflavin to produce a photodynamic reaction,7 UVC does not require a chemical substrate, making it a more convenient and potentially safer option. Cross-linking requires corneal debridement and extensive UVA exposure between 30–60 minutes,7 which can be impractical for outpatient settings.

Although accelerated cross-linking methods have shortened the treatment durations, the method is still long and invasive. UVC’s limited depth penetration into the cornea minimises risks to internal ocular structures and reduces concerns related to ultraviolet-mediated cell damage and carcinogenicity.5,6 Additionally, microorganisms are less likely to develop resistance to light-based treatments, including UVC.8

MOVING INTO CLINICAL TRIALS

As we advance in developing these groundbreaking therapies, the future for managing microbial keratitis and other localised superficial infections looks promising.

As a researcher who has had a wealth of experience in co-managing patients with corneal infections in developing countries, I find it rewarding to delve into the science behind these devastating infections and develop potential cost-effective and equitable therapeutic options.

Sanjay Marasini BOptom PhD is an emerging research fellow with the Health Research Council of New Zealand, where he leads innovative projects on nonpharmacological anti-infective technologies at the ocular surface laboratory headed by Professor Jennifer Craig at the University of Auckland.

Dr Marasini’s research expertise lies in translational biomedical science, focussing on advanced, non-pharmacological approaches to infection management.

References available at mivision.com.au.