Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies
Hong Zhu1, Irene E Kochevar2, Irmgard Behlau3
1Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States 2Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Purpose:
To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis.
Methods:
We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety.
Results:
Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea.
Conclusions:
Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.
Insights
Antimicrobial blue light (aBL) shows promise for treating infectious keratitis by significantly reducing bacterial burden. Further research is needed to confirm its safety and efficacy in human-like models.
Area of Science:
- Ophthalmology
- Microbiology
- Biomedical Engineering
Background:
- Infectious keratitis poses a significant threat to vision.
- Current treatments may have limitations, necessitating alternative therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of antimicrobial blue light (aBL) as a treatment for infectious keratitis.
- To assess the safety of aBL for retinal tissues.
Main Methods:
- Developed ex vivo rabbit and in vivo mouse models of infectious keratitis using bioluminescent Pseudomonas aeruginosa.
- Monitored infection progression noninvasively using bioluminescence imaging.
- Assessed aBL (415 nm) effectiveness and retinal safety based on radiant exposure and corneal transmission.
Main Results:
- aBL significantly reduced bacterial burden (>2-log10) in infected corneas in both models.
- Bacterial luminescence correlated linearly with colony-forming units (CFUs).
- Observed recurrence of infection in mice 24 hours post-aBL exposure; retinal toxicity depended on corneal transmission.
Conclusions:
- Antimicrobial blue light is a potential therapeutic for infectious keratitis.
- Further safety and efficacy studies in large animal models are warranted.
