EPI-ON CXL efficacy

More clinical studies with longer follow-up and especially randomised, controlled trials are required to ascertain the efficacy of “epithelium-on” corneal crosslinking (CXL) compared to the current gold standard of “epithelium-off” CXL, David O’Brart MD told delegates attending the 6th EuCornea Congress in Barcelona, Spain.

“The evidence to date shows that epi-on CXL has limited efficacy compared to epi-off CXL. Its efficacy is limited by stromal riboflavin absorption and masking of the ultraviolet absorption by the epithelium,” he said.

By contrast, there exists a large body of clinical evidence showing that traditional epithelium-off CXL is safe and effective for routine use treating keratoconus and post-LASIK ectasia, said Dr O’Brart, UK.

“Since the introduction of CXL over a decade ago there have been multiple published case series with several years follow-up, including advanced and paediatric keratoconus and other forms of ectasia which have shown stabilisation in the vast majority of cases, few complications and significant improvements in vision, topographic parameters and higher order aberrations,” he said.

These results have been confirmed by other long-term studies, some of which were randomised controlled trials, showing improvements in visual and topographic parameters up to seven and 10 years after surgery, said Dr O’Brart.

DISCOMFORT TO PATIENTS

Nevertheless, while the efficacy of CXL with the epithelium removed is not in doubt, the major downsides of the procedure are the discomfort to patients and risk of complications.

“These young patients are miserable for the immediate postoperative period, with severe postoperative pain for 24 to 48 hours, blurred vision for two to four weeks and they can’t wear their contact lenses for three to four weeks. We also see sight-threatening complications which are thankfully rare such as haze, scarring, infectious or non-infectious keratitis, persistent corneal oedema and excessive flattening,” he said.

Hence the appeal of epi-on CXL, said Dr O’Brart, with the promise of less pain, faster visual recovery, and less risk of infection as the epithelial barrier is still in place. Leaving the epithelium intact should also result in a reduced risk of stromal scarring, haze and corneal melt, with less stromal oedema and endothelial damage as well as peri-operative dehydration, he added.

Current epi-on methods that have been tried, with mixed results, include mechanical (partial epithelial disruption), chemical enhancers (benzalkonium chloride, BAC), edetate sodium (EDTA) and channel forming peptides), and iontophoresis. Investigators have also tried modifying the riboflavin solution, application time and/or the ultraviolet dosage to increase absorption of the riboflavin in the stroma, he said.

The 18 month outcomes of CXL using grid-pattern epithelial scratches and riboflavin 0.1 per cent and trometamol (Ricrolin TE) showed good improvement in visual acuity and reduction in apex power in 28 eyes, but three patients progressed after two years, said Dr O’Brart.

Another study by Filippello et al (JCRS 2012;38:283-91) found that chemical enhancement with Ricrolin was safe and well tolerated with rapid visual recovery and little postoperative pain. While the results were comparable to epi-off CXL, randomised controlled trials were needed to confirm this, said Dr O’Brart. While studies by Buzonetti (JRS 2012; 28: 763) and Caporossi (JCRS;39:1157) showed improvement in visual acuity, keratoconus progression in paediatric cases was a concern in both studies.

A literature review by Shalchi et al (Eye. 2015 Jan;29(1):15-29) concluded that while epi-on and epi-off CXL studies both showed improvement in visual acuity and refractive cylinder, Kmax worsened in most epi-off studies. However, adverse events were reported more with epithelium-off studies.

Iontophoresis, which uses electrical currents for transdermal delivery, is another promising approach to epi-on CXL, said Dr O’ Brart, but more studies are needed to determine the optimal protocol. A randomised controlled trial currently under way at St Thomas’ Hospital in London, UK, of epi-off CXL versus iontophoresis CXL (iCXL), using a modified protocol, should help to advance research in this area, he said.

“What we really need is some way of accurately assessing the cross-linking effect to be able to optimise our protocols in terms not only for epi-on and epi-off but also for accelerated CXL before we can really move ahead,” he concluded.

David O’Brart: DavidOBrart@aol.com