PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial

Abstract

Background Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment. Methods This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection. Results Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups. Conclusions PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871

Comparison between three different high fluence UVA levels in corneal collagen cross-linking for treatment of experimentally induced fungal keratitis in rabbits

“…Therefore and since 2008, CXL was intensely studied in the management of all types of microbial keratitis. 8,11,12,14 In this study that was performed on adult male New Zealand white rabbits, we found PACK-CXL alone can effectively suppress fungal infection and leads to improvement in the clinical manifestations of fungal keratitis. While comparing PACK-CXL treated groups to Voriconazole treated group, we found both to be as effective in decreasing fungal infection, improving clinical manifestations with no clinically significant difference between them.…”

“…Therefore and since 2008, CXL was intensely studied in the management of all types of microbial keratitis. 8,11,12,14…”

“…It has the advantage of treatment of mixed infections that is considered a challenging infection in most situations. 11 Likewise, CXL was previously studied and reported for microbial keratitis. 8,11–16…”

“…It has the advantage of treatment of mixed infections that is considered a challenging infection in most situations. 11 Likewise, CXL was previously studied and reported for microbial keratitis. 8,[11][12][13][14][15][16] Therefore, the aim of the current study was to compare the efficacy of CXL of 3 different total UVA fluence levels and to compare them with topical voriconazole in treatment of fungal keratitis experimentally induced in rabbits' eye based on clinical, microbiological and pathological analyses.…”

“…8,[11][12][13][14][15][16] Therefore, the aim of the current study was to compare the efficacy of CXL of 3 different total UVA fluence levels and to compare them with topical voriconazole in treatment of fungal keratitis experimentally induced in rabbits' eye based on clinical, microbiological and pathological analyses. 11…”