Original article
Argon Cold Plasma–A Novel Tool to Treat Therapy-resistant Corneal Infections

https://doi.org/10.1016/j.ajo.2018.03.025Get rights and content

Purpose

To test whether therapy-resistant corneal infections can be successfully treated with argon cold plasma to reduce or eliminate pathogen microorganisms without affecting corneal cell viability.

Design

First-in-human case series and experimental study.

Methods

Cold plasma effects on viability of primary human corneal limbal epithelial cells were studied using exposure times from 0.5 to 10 minutes (metabolic activity, oxidative stress, apoptosis). Disinfective potential of cold plasma was tested against common pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans) on culture medium and evaluated by counting colony-forming units and optical density measurements, as well as against S aureus in a human cornea infection model. Additionally, in a first-in-human trial 4 patients with therapy-resistant corneal ulcers were treated to evaluate the clinical potential of cold plasma.

Results

Cells treated for 0.5-5 minutes completely recovered within 24 hours without changes in morphology; only 10-minute treatment impaired the cells permanently. No evident oxidative stress, apoptosis, or damage to the corneal structure could be found. All pathogens were susceptible to cold plasma treatments, with different levels of sensitivity. The condition of all 4 patients significantly improved after cold plasma treatment combined with antibiotic therapy.

Conclusions

Our results indicate that argon cold plasma treatment reduces or eliminates common pathogens without impairing corneal epithelial cells in vitro, ex vivo, and in direct application on patients' eyes. We conclude that argon cold plasma therapy offers a potential supplement or alternative therapy for therapy-resistant corneal infections. A larger, comparative study is necessary to further confirm these findings.

Section snippets

Plasma Source

The plasma pen kINPen MED M12150063 used for this study was provided by neoplas tools GmbH (Greifswald, Germany) (Figure 1, Left). The plasma source consists of an operating device, a gas supply line, and the hand-pen. The plasma generation takes place in the pen itself. When a high-frequency voltage (1.1 MHz, 2-6 kV) and an argon gas flow (4-6 L/min) are applied to the plasma pen, the plasma is generated at the top of the pen and expands ouside the pen,21, 22, 23 visible as the plasma jet (

Metabolic Activity and Morphology

Metabolic activity of pHCLEC treated with cold plasma was measured over a time course of 24 hours. As shown in Figure 3 (Top row), 4 hours after plasma treatment, 100% (0.5 minute), 98% (1 minute), 90% (2 minutes), 67% (5 minutes), and 24% (10 minutes) of the initial metabolic activity could be measured in pHCLEC (as compared to negative control). Within 24 hours, cells treated for 0.5, 1, 2, and 5 minutes recovered to 130.6%, 133.4%, 125.9%, and 96.4% of the initial metabolic activity,

Discussion

Owing to the rising problem of antimicrobial resistance in many areas of medicine, including ophthalmology, the treatment of ocular infections is becoming increasingly challenging. Therefore, physical methods that do not involve the use of antibiotics are gaining attention and may offer a potential way out of the resistance dilemma.

In our study, we tested the potential of cold plasma treatment with the kINPen MED M12150063 device to counter infections of the eye while avoiding tissue damage.

The

References (32)

  • E. Martines et al.

    Towards a plasma treatment of corneal infections

    Clin Plasma Med

    (2013)
  • A. Shah et al.

    Geographic variations in microbial keratitis: an analysis of the peer-reviewed literature

    Br J Ophthalmol

    (2011)
  • D. Pascolini et al.

    Global estimates of visual impairment: 2010

    Br J Ophthalmol

    (2012)
  • T.B. Høeg et al.

    Danish Rural Eye Study: epidemiology of adult visual impairment

    Ophthalmic Epidemiol

    (2016)
  • Deutsche Ophthalmologische Gesellschaft

    Leitlinie Keratitis [Internet]

  • H. Jin et al.

    Evolving risk factors and antibiotic sensitivity patterns for microbial keratitis at a large county hospital

    Br J Ophthalmol

    (2017)
  • D. Miller

    Update on the epidemiology and antibiotic resistance of ocular infections

    Middle East Afr J Ophthalmol

    (2017)
  • W. Haas et al.

    Monitoring antibiotic resistance in ocular microorganisms: results from the Antibiotic Resistance Monitoring in Ocular micRorganisms (ARMOR) 2009 surveillance study

    Am J Ophthalmol

    (2011)
  • L. Hazlett et al.

    Challenges of corneal infections

    Expert Rev Ophthalmol

    (2016)
  • B. Haertel et al.

    Non-thermal atmospheric-pressure plasma possible application in wound healing

    Biomol Ther (Seoul)

    (2014)
  • H. Manner et al.

    Prospective evaluation of a new high-power argon plasma coagulation system (hp-APC) in therapeutic gastrointestinal endoscopy

    Scand J Gastroenterol

    (2007)
  • J. Gugenheim et al.

    A randomized controlled trial comparing fibrin glue and PlasmaJet on the raw surface of the liver after hepatic resection

    Hepatogastroenterology

    (2011)
  • J.L. Glover et al.

    The plasma scalpel: a new thermal knife

    Lasers Surg Med

    (1982)
  • M. Zenker

    Argon plasma coagulation

    GMS Krankenhhyg Interdiszip

    (2008)
  • R. Matthes et al.

    Antimicrobial efficacy of an atmospheric pressure plasma jet against biofilms of Pseudomonas aeruginosa and Staphylococcus epidermidis

    Plasma Process Polym

    (2013)
  • J. Lademann et al.

    Comparison of the antiseptic efficacy of tissue-tolerable plasma and an octenidine hydrochloride-based wound antiseptic on human skin

    Skin Pharmacol Physiol

    (2012)

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