Do You Need to Travel Overseas for C3-R Cross-Linking?

Every few weeks I meet a keratoconus patient, or the parent of one, who has been reading about C3-R and is weighing up a trip to Beverly Hills. They’ve learned that it’s the gentle, epithelium-on version of cross-linking, the one that doesn’t scrape the surface of the eye, and they’ve concluded that gentle means overseas.

The instinct is right. The trip isn’t necessary. The same category of treatment, in a more advanced form with FDA Phase 3 evidence and a larger published dataset behind it, is available in Brisbane with a Medicare rebate. Patients travel here for it from across Australia and from overseas. This post lays out the evidence so you can judge for yourself.

What C3-R is

C3-R, marketed as Holcomb C3-R, is the brand name for the transepithelial riboflavin cross-linking that Dr Brian Boxer Wachler developed in Beverly Hills in 2003 and offers exclusively at his institute. Its appeal is simple. In the original cross-linking method the epithelium, the cornea’s thin surface skin, is removed so the riboflavin can soak into the tissue underneath. That works, but the raw surface is what makes the first few days painful and slows recovery. Epi-on cross-linking leaves the surface intact.

Those advantages are real and they belong to epi-on cross-linking in general, not to any one brand. A 2021 systematic review pooling the published comparisons found epi-on treatment carried less risk of delayed healing and persistent haze than epi-off, with less pain and fewer surface complications.

Where early epi-on struggled, and how that was solved

The same review found the catch. At twelve months, 7% of eyes treated with the older epi-on methods had progressed, against 2% after epi-off. The reason is chemistry. Cross-linking works by ultraviolet light activating riboflavin in the presence of oxygen, and an intact epithelium is a barrier to both the riboflavin and the oxygen. Early transepithelial protocols simply delivered a weaker treatment.

The fix was engineering rather than branding: a riboflavin formulation designed to cross the epithelium, supplemental oxygen delivered through goggles during the treatment, and higher-intensity pulsed ultraviolet light that lets oxygen replenish between pulses. That is the approach the US Food and Drug Administration examined in Glaukos Epioxa. In its Phase 3 trials the treatment met its primary endpoint, flattening the steepest part of the cornea by 1.0 dioptre relative to untreated control eyes, and on 20 October 2025 the FDA approved Epioxa as the first incision-free cross-linking treatment, for patients aged thirteen and over. I was the first surgeon in Australia to perform it, back when it was called Boost under Avedro, and I’ve offered it in Brisbane for years. There’s more on the Epioxa story elsewhere on this site.

Treating the cone, not the whole cornea

Epi-on solved the recovery problem. Topography-guided treatment goes after the disease itself.

Standard cross-linking, epi-on or epi-off, treats the whole cornea with one broad beam of ultraviolet light. Keratoconus isn’t a whole-cornea disease, though. It’s a cone, a localised area of weakness and steepening, usually below the centre. Topography-guided cross-linking uses your corneal map to concentrate the ultraviolet energy on the cone, delivering more stiffening where the cornea is weakest and less where it’s healthy.

I do this on the Glaukos Mosaic system. I was one of fourteen surgeons worldwide given early access to the platform, and it remains the only topography-guided cross-linking machine in Australia. The published evidence for the approach includes a prospective series of 42 eyes treated with epi-on, oxygen-supplemented, customised cross-linking that reported improved uncorrected and corrected vision and significant corneal flattening at one year, with no adverse events.

What our own published data shows

The results of my technique, combining Mosaic topography-guided treatment with oxygen goggles and pulsed epi-on irradiation, are published in the Journal of Cataract and Refractive Surgery (Cronin, Gunn and Chang, 2024). It’s the largest dataset of this procedure published anywhere in the world: 102 eyes of 80 patients followed for about a year.

The numbers are worth reading slowly, because they show something standard cross-linking isn’t designed to deliver:

• Kmax, the steepest point of the cornea and the standard measure of keratoconus progression, went from 53.0 dioptres to 51.9. Cross-linking’s job is to stop that number rising. Here it fell by more than a dioptre on average.
• Mean corneal curvature fell from 46.2 to 45.8 dioptres.
• Best corrected vision improved from 0.18 to 0.07 logMAR on average, roughly a line on the chart, and 60% of patients saw better with their glasses or lenses after treatment than before.

Stability was the goal. Improvement was the result. That’s the difference the customised pattern makes.

How that compares with what C3-R has published

I want to be fair here, because C3-R has been around a long time and its clinic reports excellent results. So I’ll stick to what is in the peer-reviewed literature.

The published record for C3-R that I can find consists of a 2007 retrospective series in the Journal of Cataract and Refractive Surgery comparing 12 eyes treated with Intacs ring segments alone against 13 eyes treated with Intacs plus C3-R, which found that adding C3-R enhanced the effect of the rings, and a 2010 letter in the same journal arguing that the transepithelial technique is effective. The 99.3% stability figure that appears on the clinic’s website is one I haven’t been able to find in a peer-reviewed publication.

Set that against what stands behind the treatment in Brisbane: a multicentre FDA Phase 3 programme for the epi-on oxygen-enhanced method, an independent 42-eye prospective series for the customised version, and our own 102-eye series in the same journal reporting not just stability but flattening and better vision. I’m not saying C3-R doesn’t work. I’m saying that the evidence for what we do here is larger, more recent, independently replicated, and reports better outcomes than anything C3-R has published.

People travel to Brisbane, not from it

The traffic runs the other way. Patients come to us for this treatment from every part of Australia and from overseas, because the combination of oxygen-enhanced epi-on treatment and topography guidance on the Mosaic isn’t offered anywhere else in the country as far as I’m aware. It’s a day procedure. Most interstate patients fly in, have their assessment and treatment, and fly home within the week, and we plan the follow-up scans around their travel. The travelling to see Dr Cronin page covers clinics, timelines and the travel subsidies that may apply.

If you’ve been told keratoconus is progressing and you’ve been researching C3-R, you were looking for the right thing. You just don’t have to leave the country to get it, or a better version of it.