CXL long-term

Frederik Raiskup MD, PhD, FEBO 

Corneal crosslinking (CXL) has been proven to be a safe and effective means of treating keratoconus over the long-term, Frederik Raiskup MD, PhD, FEBO told delegates attending the 6th EuCornea Congress in Barcelona, Spain.

“I think when we look at the evidence in the scientific literature and consider that it is now over 16 years since the first CXL procedure was performed in human eyes, we are justified in speaking about long-term results for this procedure,” he said.

Discussing the clinical results of epithelial-off CXL, Dr Raiskup, Carus University Hospital, Dresden, Germany, said that a cursory examination of PubMed shows that interest in the procedure shows no sign of diminishing.

“Last year (2014) there were around 850 papers on this topic, whereas today another 250 papers have been added to the list and the trend shows no sign of slowing down,” he said.

While many of these papers were non-randomised case series or retrospective studies, a number of randomised controlled trials have been conducted in recent years, added Dr Raiskup.

The study by Wittig-Silva et al (Ophthalmology. 2014 Apr;121(4):812-21) for instance recently presented three years’ results of a prospective, randomised controlled trial of 94 eyes, 48 in the control group and 46 in the treatment group.

SUSTAINED IMPROVEMENT

“The conclusion at 36 months was that there was a sustained improvement in maximum simulated keratometry values (Kmax), uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) after CXL, whereas eyes in the control group demonstrated further progression of keratoconus,” he said.

The evidence, however, was less clear-cut in a review and meta-analysis by Craig et al (Ocul Surf. 2014 Jul;12(3):202-14), said Dr Raiskup.

Their literature search identified 3,400 records of which 49 were considered for inclusion in the meta-analysis. The majority of the studies (39/49) were graded as very low quality evidence. While statistically significant improvements were found in all efficacy outcomes at 12 months after the operation, the authors noted that “uncertainty remains about the duration of benefit”.

Another wide-ranging review by Hamada et al for the Cochrane Collaboration (Cochrane Database Syst Rev. 2015 Mar 24;3) analysed data from 219 eyes drawn from three randomised controlled trials of CXL. The study concluded that the evidence for the use of CXL in the management of keratoconus is limited due to the lack of properly conducted randomised controlled trials.

A more recent study by O’Brart et al (Am J Ophthalmol. 2015 Aug 22. pii: S0002-9394(15)00517-6) reported that improvements in topographic and wavefront parameters evident at one year after CXL continued to improve at five years and were maintained at seven years.

The conclusions of O’Brart’s study were also echoed in the 10-year results published by Dr Raiskup’s own group in 2015 (Journal of Cataract & Refractive Surgery, Volume 41, Issue 1, 41-46) of 34 eyes of 24 patients which found that CXL was safe and effective in treating progressive keratoconus and achieving long-term stabilisation of the condition.

Good results have also been obtained in paediatric patients, said Dr Raiskup.
“We know these patients are at high risk because of the very fast progression of keratoconus and increased probability of the need for
corneal transplant.”

In a study carried out by Caporossi et al (Cornea. 2012 Mar;31(3):227-31), 152 patients with progressive keratoconus aged 18 years or younger (range 10-18 years) demonstrated significant and rapid functional improvement and stable outcomes up to three years after CXL treatment.

The evidence for the efficacy of so-called accelerated CXL, which shortens the illumination time by increasing the illumination intensity and reduces the overall treatment time, was less convincing, said Dr Raiskup.

“This works well in theory, but when we perform these experiments on animal corneas, we see that the biomechanical effect is limited up to the intensity of around 45mW/cm2. Studies by Hammer et al (Invest Ophthalmol Vis Sci. 2014 May 2;55(5):2881-4) also showed that the biomechanical effect of CXL decreased significantly when high irradiance and shorter irradiation time settings were used,” he said.

OXYGEN CONSUMPTION

The Hammer study also identified increased oxygen consumption associated with higher irradiances as a potentially cause of reduced treatment efficiency, said Dr Raiskup. He said that more controlled, randomised studies were needed to properly assess the safety and efficacy of accelerated CXL.

Dr Raiskup also noted that a few recent studies have underscored the cost-effectiveness of CXL compared with standard management for the treatment of progressive keratoconus.

He concluded by citing the results of a 2015 study by Sandvik et al (Cornea. 2015 Sep;34(9):991-5), which reported that the frequency of keratoplasty for keratoconus had been more than halved in their department over the last decade.

“The authors concluded that there is reason to believe that this reduction is for a great part caused by the introduction of CXL treatment. I think this confirms what we are seeing ourselves in our own clinic,” he said.

Frederik Raiskup: frederik.raiskup@uniklinikum-dresden.de