A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthameoba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) Study.

Background: Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro Rose Bengal Photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates. 22,23 In one published series RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthameoba keratitis not responsive to medical therapy. Methods: This international, randomized, sham and placebo controlled 2-arm clinical trial, randomizes patients with smear positive fungal and acanthameoba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) Topical antimicrobial plus sham RB-PDT or 2) Topical antimicrobial plus RB-PDT Discussion: We anticipate that RB-PDT will improve best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via clinicaltrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. Trial Registration: NCT, NCT05110001, Registered November 5, 2021. https://www.clinicaltrials.gov/study/NCT05110001.

Effect of Simultaneous Endothelial Keratoplasty and Cataract Surgery: A Secondary Analysis of the Descemet Endothelial Thickness Comparison Trial.

PURPOSE: Combining cataract surgery with endothelial keratoplasty (triple EK) is a common practice and may be safer because it commits the patient to only one surgery. This study aimed to determine whether outcomes of pseudophakic endothelial keratoplasty and triple EK have similar outcomes. METHODS: This was a non-prespecified secondary analysis of a multicenter, double-masked, randomized, controlled clinical trial. Enrollment centers included the Casey Eye Institute at Oregon Health and Sciences University and the Byers Eye Institute at Stanford University. Patients with damaged or diseased endothelium and were considered good candidates for either Descemet membrane endothelial keratoplasty or ultrathin Descemet stripping automated endothelial keratoplasty were randomized to one of the two surgeries 1-2 days prior to surgery. If the patient had a cataract, they underwent simultaneous cataract surgery. The primary outcome was visual acuity at 6 months. Visual acuity at 3, 12, and 24 months, 3, 6, 12, and 24 month endothelial cell density and intraoperative and postoperative complications were also recorded. RESULTS: Those who had pseudophakic EK generally were older, more likely to be male, and more likely to have worse baseline vision with higher corneal densitometry values. After controlling for baseline visual acuity and type of keratoplasty, those that underwent Triple-EK had 0.09 better LogMAR lines better visual acuity at 6 (95% CI -0.17 to -0.10; P = 0.02) and 12 months (95% CI -0.21 to -0.07; P = 0.03). Although those receiving Triple- EK had nearly one-half LogMAR line better visual acuity at 24 months, it was no longer statistically significant (95% CI -0.20 to -0.05; P = 0.36). There was no statistically significant difference in ECD between groups at any timepoint. Those undergoing triple EK were more likely to have at least one adverse event (P = 0.02). CONCLUSIONS: Earlier intervention with Triple-EK may improve visual acuity outcomes after endothelial keratoplasty compared with staged procedures, but may also increase the risks of adverse events including the need for re-bubble.

Ocular Rosacea microBiome Study (ORBS)-sub-microbial versus antibiotic dosing of doxycycline versus placebo in treatment of symptomatic ocular rosacea: study protocol for a parallel-arm randomized clinical trial.

BACKGROUND: Ocular rosacea is common and is often managed with long-term antibiotic treatment. Doxycycline is the most commonly selected antibiotic for the treatment of rosacea. As there is no established standard of care treatment dose for rosacea, prescribed doses of doxycycline vary widely. The FDA classifies 40 mg daily dose of doxycycline for ocular rosacea as sub-microbial in comparison to an antibiotic dose of 200 mg daily. However, this "sub-microbial" dose has never been evaluated in patients with ocular rosacea, and even the sub-microbial dose has potential to alter systemic mucosa flora. Here, we present a randomized controlled trial using RNA sequencing to fully characterize the impact of sub-microbial antibiotic dosing of doxycycline on antimicrobial resistance and bacterial composition of the ocular and gut flora. METHODS: In a triple-masked parallel randomized control trial, patients with ocular rosacea will be randomized to three arms: a 40-mg dose of doxycycline, a 200-mg antibiotic dose of doxycycline, or placebo. Collected rectal and lower eyelid samples will be compared for frequency of antimicrobial resistance genetic determinants and microbiome diversity. A subjective ocular surface disease index survey and objective tear breakup time measurement will be determined. DISCUSSION: These results will enhance our understanding of the overall systemic impact of long-term systemic sub-microbial antibiotic dosing for the treatment of chronic recurrent ocular inflammatory diseases. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.org (NCT05296837) on March 22, 2022.