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Corneal cross-linking for treating infectious keratitis: final results of the prospective randomized controlled multicenter trial

Poster Details

First Author: E.Torres-Netto SWITZERLAND

Co Author(s):    R. Shetty   B. Knyazer   S. Chen   M. Hosny   F. Gilardoni   F. Hafezi     

Abstract Details


Severe visual impairment due to corneal infection is a major cause of global blindness. The socioeconomic costs related to corneal ulcers and their treatment are immense. PACK-CXL (photoactivated chromophore for infectious keratitis-corneal cross-linking), in contrast, does not generate massive costs, but rather uses Vitamin B2 solution and a light source. In addition, previous data show that PACK-CXL is also efficient in antibiotic-resistant infections. Our objective was to analyze the time to corneal epithelization with PACK-CXL as a first-line treatment in early infectious corneal ulcers, and compare it to the current standard of care, antimicrobial therapy.


The final phase of this study was conducted jointly by the Center for Applied Biotechnology and Molecular Medicine at the University of Zurich (Zurich, Switzerland), the Narayana Nethralaya Eye Hospital (Bangalore, India), the Ben-Gurion University of the Negev Sheva (Beer-Sheva, Israel), the Wenzhou Medical University (Wenzhou,China) and Cairo University (Cairo,Egypt).


This is a prospective, interventional, multicenter, randomized controlled phase-III clinical trial. The inclusion criteria were infiltrates and early ulcers up to 4mm in diameter and 300μm depth. If patient was on antibiotic/antifungal therapy, it was interrupted at least one day prior to PACK-CXL treatment. Patients were randomized into two groups: PACK-CXL only or Medication (antimicrobial) only. In the PACK-CXL group, epithelial removal around the borders was followed by application of riboflavin and irradiation with UV-A (total energy 5.4 or7.2J/cm2). The Medication group received the current standard of care, antimicrobial therapy. Time of corneal re-epithelialization was compared in both groups.


Forty-two patients were included, twenty-three in the Medication group and nineteen in the PACK-CXL group. Five cases of treatment failure were observed and excluded from the final analysis: three patients in the Medication group required corneal transplantation due to descemetocele and corneal perforation and two patients in PACK-CXL group needed additional antimicrobial therapy. Gram-positive cocci were the most commonly identified pathogens. Cases of fungal infection were shown to have worse visual acuity both at presentation and at discharge. No significant differences in corneal re-epithelization time were observed between Medication and PACK-CXL groups (respectively, 15.515.0 vs 10.77.7 days, p=0.791).


Our results suggest a role for PACK-CXL as an alternative to antimicrobials as primary treatment for infectious corneal infiltrates and early corneal ulcers. Even with a tendency for a longer healing (non-significant difference of 5 days), 89% of eyes treated with PACK-CXL healed without the use of antimicrobial therapy, compared to 93% in the Medication (antimicrobial)-only group. While the results of this multicenter randomized controlled trial are promising, a larger sample is needed to further investigate the efficacy and safety of this treatment modality, especially in fungal infections.

Financial Disclosure:

has significant investment interest in a company producing, developing or supplying product or procedure presented, receives non-monetary benefits from a company producing, developing or supplying the product or procedure presented

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