EPI-ON CXL

A new collagen cross-linking technique (CXL) that uses iontophoresis to enhance penetration of riboflavin through epithelial tissue may enable patients to undergo the procedure without the need for epithelial debridement, said Francois Malecaze MD, CHU de Toulouse-Hopital Purpan, Toulouse, France, at Femto 2013, an international meeting on anterior segment surgery. “The iontophoresis technique could allow intrastromal riboflavin diffusion, while keeping the corneal epithelium on, combining the efficiency of the standard procedure without the side effects of epithelial debridement,” noted Dr Malecaze.

Less pain

He presented results from a rabbit eye study which indicated that the new and as yet experimental “epi-on” crosslinking technique allows penetration of riboflavin into the corneal stroma for CXL. He also reported that preliminary results from a clinical study show that it causes patients much less pain than is the case with conventional “epi-off” techniques. The current CXL technique requires the debridement of the epithelium to allow the penetration of riboflavin into the cornea. That causes patients significant pain during the first two postoperative days and results in some loss of visual acuity for the first three postoperative months. It also creates the risk of more serious complications such as infection and stromal opacity due to corneal scarring.

The new technique proposed by Dr Malecaze and his associates involves iontophoresis, a technique that has been developed for enhancing the diffusion of ionised molecules through living tissue using a small electric charge. It also involves the use of special formulations of riboflavin Ricrolin TE (Sooft Italia) that has been modified to enhance penetration through the epithelium. “Riboflavin is a perfect candidate for delivery through iontophoresis because it has a small molecular weight, is negatively charged at physiologic pH, is soluble in water and has minimal buffer content,” Dr Malecaze said.

The iontophoretic CXL technique involves placement of two electrodes, one on the forehead and the other inside a reservoir cup fixed to the cornea by means of suction ring. The generator applies a constant current of 1mA for a preset period of five minutes allowing riboflavin in the reservoir to diffuse through the anterior stromal tissue. Afterwards the cornea is irradiated with UVA in the usual manner. In an animal study involving rabbits that underwent the iontophoretic CXL procedure HPLC biochemical analysis and two-photon microscopy showed that although riboflavin only penetrated to half the depth of that achieved with the conventional epi-off technique, the diffusion of the agent was sufficient to achieve adequate cross-linking in the anterior two-thirds of the stroma.

Resolved in 24 hours

The preliminary results of an ongoing multicentre clinical study that has so far involved 30 patients undergoing iontophoretic CXL show that all patients had a punctate keratitis postoperatively similar to photokeratitis, and around half of patients had pain five hours after the procedure, but it resolved within 24 hours. In addition, the cornea had a normal appearance under slit-lamp examination. “Since we have only two months’ work it is too early to draw any conclusions about the efficacy of the technique,” Dr Malecaze added.