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CXL for infectious keratitis

DMEK shows good graft survival and visual outcomes at five years.

Roibeard O’hEineachain

Posted: Friday, June 5, 2020

PACK-CXL (photo-activated chromophore for infectious keratitis-corneal cross- linking) appears to be an effective alternative to standalone treatment for infectious corneal infiltrates and early corneal ulcers, according to the preliminary results of a phase-III RCT (randomised controlled trial) presented by Emilio Torres-Netto MD, at the 24th ESCRS Winter Meeting in Marrakech, Morocco.

“Even with a tendency for a longer healing, 85% of eyes treated with PACK-CXL healed without the use of antimicrobial therapy,” said Dr Torres-Netto, ELZA Institute and University of Zurich, Zurich, Switzerland.

The prospective multi-centre, randomised controlled trial involved 30 patients with infectious keratitis. All had infiltrates and early ulcers up to 4mm in diameter and 350μm in depth. Gram-positive cocci were the most commonly identified pathogens. there were also five case of filamentous fungal keratitis (Aspergillus sp), he noted.

The study randomised patients to two treatment groups, namely PACK-CXL or the current standard of care, antimicrobial therapy. Patients already receiving antibiotic or antifungal therapy stopped their treatment at least one day before undergoing their assigned treatment. Prior to treatment, the mean infiltrate size was 1.8mm for the medication group and 2.4 mm for the PACK-CXL group (p=0.113).

“Our objective was to analyse the time to corneal epithelialisation with PACK-CXL as a first-line treatment in early infectious corneal ulcers and compare it to the current standard of care, antimicrobial therapy,” Dr Torres-Netto said.

In the PACK-CXL group, removal of the epithelium around the borders of the ulcerations was followed by application of a riboflavin and irradiation with UV-A (total energy 5.4 or 7.2J/cm2), Dr Torres-Netto explained.

He noted that there was no significant difference between the groups in terms of corneal re-epithelisation time, which was 12.3 days in PACK-CXL group and 6.8 days for standard treatment. One patient in the medication group developed a corneal perforation on the eleventh day after initiation of antibiotic therapy and one patient in the PACK-CXL group developed fungal keratitis and received antifungals from day four of the study. Both patients were excluded from the analysis. However, he noted that even on an intent-to-treat basis the PACK-CXL was effective in 85% of patients.

The need for new treatments

Dr Torres-Netto noted that infectious keratitis due to corneal infection is a major cause of global blindness and severe visual impairment. The socioeconomic costs related to corneal ulcers and their treatment are immense. In addition, antibiotic resistance has become a global problem and the development of new antibiotics has been at a virtual standstill for decades.

“One of the most recent antibiotics that we have today are the fluoroquinolones and in some series we have already 50% resistance in patients with chronic use of fourth-generation fluoroquinolones, so it’s a great concern at this time,” he added.

He pointed out that PACK-CXL – a new term to distinguish the use of CXL for infectious keratitis treatment from its use for corneal ectatic disorders – does not require expensive medication, but only Vitamin B2 solution and a UV light source. In addition, previous data show that PACK-CXL may also be efficient in antibiotic-resistant and mixed infections.

Size of lesions determines speed of re-epithelialisation

In addition, a soon-to-be published meta-analysis of studies involving PACK-CXL appears to support the present study’s findings. The meta-analysis included only studies involving the use of the therapy for infectious keratitis with robust reporting of epithelial healing times and comprised four studies and 12 case reports and case series. In those studies, the re-epithelialisation times following PACK-CXL were similar to those in the current study, except one study where CXL was combined with antibiotics but in which 70% of the infections were of fungal origin.

A further meta-analysis including the present study looking at 72 eyes in all showed no significant difference between PACK-CXL with antibiotics and PACK-CXL without antibiotics in terms of the likelihood of successful re-epithelialisation. The only significant factor found to affect the success of treatment was the diameter of the lesion, which had inverse correlation with re-epithelialisation time. Therefore, treatment should commence as early as possible, he said.

“Our results suggest that PACK-CXL may become an alternative standalone treatment for infectious corneal infiltrates and early corneal ulcers. While the preliminary results of this multi-centre randomised trial are promising, a larger sample is needed to further investigate the efficacy and safety of this treatment modality,” Dr Torres-Netto said.

This preliminary phase of the study was led by the ELZA Institute in Zurich, Switzerland and conducted jointly with the Centre 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) and the Wenzhou Medical University (Wenzhou, China).


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