Enhancing Rose Bengal penetration in <i>ex vivo</i> human corneas using iontophoresis
Creators: name: Lai, James M
name: Chen, Justin
name: Navia, Juan Carlos
name: Durkee, Heather
name: Gonzalez, Alex
name: Rowaan, Cornelis
name: Arcari, Timothy
name: Aguilar, Mariela C
name: Llanes, Katrina
name: Ziebarth, Noel
name: Martinez, Jaime D
name: Miller, Darlene
name: Flynn, Harry W
name: Amescua, Guillermo
name: Parel, Jean-Marie
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Space Science
subject: Medicine
subject: Cell Biology
subject: Physiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Science Policy

description: <b>Aim:</b> Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) has poor corneal penetration, limiting its efficacy against acanthamoeba keratitis (AK). Iontophoresis enhances corneal permeation of charged molecules, piquing interest in its effects on RB in <i>ex vivo</i> human corneas. <b>Methods:</b> Five donor whole globes each underwent iontophoresis with RB, soaking in RB, or were soaked in normal saline (controls). RB penetration and corneal thickness was assessed using confocal microscopy. <b>Results:</b> Iontophoresis increased RB penetration compared with soaking (177 ± 9.5 μm vs. 100 ± 5.7 μm, <i>p</i> &lt; 0.001), with no significant differences in corneal thickness between groups (460 ± 87 μm vs. 407 ± 69 μm, <i>p</i> = 0.432). <b>Conclusion:</b> Iontophoresis significantly improves RB penetration and its use in PDAT could offer a novel therapy for acanthamoeba keratitis. Further studies are needed to validate clinical efficacy. The study aimed to improve a new treatment for eye infections known as photodynamic antimicrobial therapy. It investigated whether the use of electricity through a technique called iontophoresis could help a chemical called Rose Bengal go deeper into the eye in order to target more severe infections. The iontophoresis machine was custom built, with patient-contacting components 3D printed. The experiments were performed using donated human eye tissue and found that iontophoresis significantly improved the penetration depth of Rose Bengal as compared with the current technique of only soaking the eye in Rose Bengal. Infectious keratitis poses a significant global threat to vision, with <i>Acanthamoeba</i> keratitis (AK) often presenting as deep and severe infection, refractory to medical therapy. Current treatments for AK are limited, necessitating investigation into alternative therapies such as Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) and Photo Activated Chromophore for Keratitis-Corneal Cross Linking (PACK-CXL). RB-PDAT shows promise but faces challenges due to limited corneal penetration, suggesting the need for methods like iontophoresis to enhance drug delivery into the cornea. This study aims to investigate the efficacy of iontophoresis in improving RB penetration depth in <i>ex vivo</i> human corneas, potentially offering a novel approach to treating severe AK. Iontophoresis for RB corneal delivery is achieved using a custom-built, handheld device, applying a reservoir of the drug through a 3D printed cathode. The system controls drug delivery by adapting the electric field based on specific resistance, allowing constant current delivery of 2.5 mA. Human globes are prepared within 24 h post-mortem, undergoing de-epithelialization before iontophoresis, with a total of 15 human globes (5 iontophoresis, 5 soak only, 5 control) prepared and followed by corneal imaging via confocal microscopy to assess penetration depth. Iontophoresis increased RB penetration compared with soaking (177 ± 9.5 μm vs. 100 ± 5.7 μm, <i>p</i> &lt; 0.001), with no significant differences in corneal thickness between groups (460 ± 87 μm vs. 407 ± 69 μm, <i>p</i> = 0.432). The use of iontophoresis is promising for targeting severe AK cases by enhancing Rose Bengal penetration depth, potentially addressing issues of medical treatment failure. The development of a custom iontophoresis device utilizing 3D printing technology presents advantages for future clinical applications, particularly in low-resource settings, with considerations for patient safety and feasibility of implementation.