Rose Bengal Photodynamic Antimicrobial Therapy: A Novel Treatment for Resistant Fusarium Keratitis

Amescua, Guillermo; Arboleda, Alejandro; Nikpoor, Neda; Durkee, Heather; Relhan, Nidhi; Aguilar, M.; Flynn, Harry W.; Miller, Darlene; Parel, Jean Marie

doi:10.1097/ico.0000000000001265

Cited by 68 publications

(45 citation statements)

References 9 publications

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“… 20 The effect and toxicity of RB in corneal crosslinking has also been well established in preclinical studies, 11 , 21 and experience with RB plus green light is being accumulated in human studies. 6 – 8 …”

Section: Discussionmentioning

confidence: 99%

“… 25 One advantage of Rose Bengal is its long history of use in human corneal tissue, several demonstrated light-initiated corneal applications in preclinical studies, and recent clinical studies in human patient's cornea. 6 – 8 …”

Section: Discussionmentioning

confidence: 99%

“… 1 – 5 Recently, the first uses of RB photosensitization in a human patient's cornea was reported. 6 – 8 The treatment halted a sight-threatening case of fusarium keratitis and, 16 months later, the cornea showed a persistent demarcation line in optical coherence tomography (OCT), a classical sign of corneal crosslinking. 7 …”

Section: Introductionmentioning

confidence: 99%

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Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Wertheimer

Mendes

Pei

et al. 2020

Trans. Vis. Sci. Tech.

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Oxygen-independent cornea crosslinking (CXL) using rose bengal (RB) and green light may have unique clinical applications. These studies were designed to gain insight into the arginine (arg)-enhanced anaerobic crosslinking process, to maximize crosslinking efficiency, and to test a clinically feasible method for oxygen-free CXL. Methods: Rabbit corneas were treated ex vivo using 1 mM RB and 532 nm light. RB photodecomposition, monitored by absorption spectrophotometry, was used to optimize arg concentration and to develop an irradiation and re-dying protocol. The minimal effective green light fluence was identified by linear tensile strength measurements. RB penetration into the stroma was determined by fluorescence microscopy. To favor the anaerobic pathway, a contact lens was used to minimize stromal oxygen level during irradiation. Stromal cell toxicity was evaluated by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Results: RB photodecomposition reached 75% of its maximal effect at 200 mM arg and the optimal fluence increment was 32.7 J/cm 2. The minimal effective fluence for cornea stiffening was 65.4 J/cm 2. Placement of a contact lens promoted oxygen-independent cornea stiffening, similar to that obtained on isolated, oxygen-deprived cornea. RB penetration into the stroma with arg present was limited to ∼120 μm, about 25% deeper than without arg. Stromal cell toxicity was limited to the depth of RB and arg penetration. Conclusions: An oxygen-independent pathway in cornea for RB-CXL was characterized and optimized, including a possible clinical protocol for its use. Translational Relevance: Oxygen-independent RB-CXL is an efficient and effective process that can be developed further for unique clinical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Wertheimer

Mendes

Pei

et al. 2020

Trans. Vis. Sci. Tech.

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“…The use of rose bengal PDT is gaining traction as a viable alternative to conventional treatments of fungal infections, with a recent case report on its use for Fusarium keratitis . An in vitro study also established the efficacy of photoactivated rose bengal against the dermatophyte, Trichophyton rubrum , the main causative agent of onychomycosis .…”

Section: Introductionmentioning

confidence: 99%

Genetic Tolerance to Rose Bengal Photodynamic Therapy and Antifungal Clinical Application for Onychomycosis

Houang

Perrone

Pedrinazzi

et al. 2018

Advanced Therapeutics

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Photodynamic therapy (PDT) with rose bengal has seen increasing use in clinical applications and has shown effective antifungal capacity in vitro. However, there is limited understanding of the effects of this emerging therapy at a genetic level. A rose bengal PDT screen using a green laser (λ = 532 nm) on the entire non-essential gene library of the model organism, Saccharomyces cerevisiae, and a subsequent pilot patient study (n = 6 patients) in the treatment of onychomycosis caused by Trichophyton rubrum is reported. Of the 4800 yeast strains screened, 482 sensitive and 175 resistant strains are identified. The key biochemical pathways found to be affected included ergosterol biosynthesis, vacuolar acidification, and purine/S-adenosyl-l-methionine biosynthesis. The implications of these findings inform the clinical application of an optimized rose bengal PDT protocol involving nail treatment with a rose bengal solution (140 µm) and green light irradiation (fluence 763 J cm −2 ). All patients achieved complete cure within three to five treatment sessions in the absence of pain or other side effects. The outcome of the genetic screen may thus inform the development of more efficient clinical treatments using rose bengal PDT, as demonstrated in the successful treatment of onychomycosis.

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“…There has been a wide variety of PS structures that have been reported to be effective in aPDI 4 , 5 , including well established dyes such as the phenothiazinium salt methylene blue 6 , xanthenes such as Rose Bengal 7 , and carbocyanines such as indocyanine green 8 . Moreover a host of newer cationic derivatives of tetrapyrrole structures (porphyrins 9 , phthalocyanines 10 , and bacteriochlorins 11 ) have been reported to have very high activities.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Photodynamic Inactivation Mediated by Tetracyclines in Vitro and in Vivo: Photochemical Mechanisms and Potentiation by Potassium Iodide

Xuan

Huang

et al. 2018

Sci Rep

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Tetracyclines (including demeclocycline, DMCT, or doxycycline, DOTC) represent a class of dual-action antibacterial compounds, which can act as antibiotics in the dark, and also as photosensitizers under illumination with blue or UVA light. It is known that tetracyclines are taken up inside bacterial cells where they bind to ribosomes. In the present study, we investigated the photochemical mechanism: Type 1 (hydroxyl radicals); Type 2 (singlet oxygen); or Type 3 (oxygen independent). Moreover, we asked whether addition of potassium iodide (KI) could potentiate the aPDI activity of tetracyclines. High concentrations of KI (200–400 mM) strongly potentiated (up to 5 logs of extra killing) light-mediated killing of Gram-negative Escherichia coli or Gram-positive MRSA (although the latter was somewhat less susceptible). KI potentiation was still apparent after a washing step showing that the iodide could penetrate the E. coli cells where the tetracycline had bound. When cells were added to the tetracycline + KI mixture after light, killing was observed in the case of E. coli showing formation of free molecular iodine. Addition of azide quenched the formation of iodine but not hydrogen peroxide. DMCT but not DOTC iodinated tyrosine. Both E. coli and MRSA could be killed by tetracyclines plus light in the absence of oxygen and this killing was not quenched by azide. A mouse model of a superficial wound infection caused by bioluminescent E. coli could be treated by topical application of DMCT and blue light and bacterial regrowth did not occur owing to the continued anti biotic activity of the tetracycline.

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Rose Bengal Photodynamic Antimicrobial Therapy: A Novel Treatment for Resistant Fusarium Keratitis

Cited by 68 publications

References 9 publications

Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Arginine as an Enhancer in Rose Bengal Photosensitized Corneal Crosslinking

Genetic Tolerance to Rose Bengal Photodynamic Therapy and Antifungal Clinical Application for Onychomycosis

Antimicrobial Photodynamic Inactivation Mediated by Tetracyclines in Vitro and in Vivo: Photochemical Mechanisms and Potentiation by Potassium Iodide

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