For more than a decade, epi-on cross-linking has promised a gentler way to treat keratoconus. It strengthens the cornea without first removing its outer layer, the epithelium. The catch has been that earlier versions produced a weaker stiffening effect. Speaking to Healio | Ocular Surgery News at the ESCRS 2026 congress in London, Prof. Farhad Hafezi said that with the ELZA epi-on protocol, which needs neither iontophoresis nor extra oxygen, “epi-on is really happening.”

In the short video interview, Prof. Hafezi, Chief Medical Officer of the ELZA Institute, and Nikki Hafezi, its Chief Executive Officer, looked back on the 44th ESCRS Congress (11–15 September 2026). They also looked ahead. By Prof. Hafezi’s count, ELZA was represented with 22 contributions.

New cross-linking papers

Corneal cross-linking (CXL) treats keratoconus, in which the cornea thins, bulges into a cone and blurs vision. Riboflavin (vitamin B2) drops soak into the cornea and are then activated with ultraviolet-A (UV-A) light. This stiffens the tissue and halts the disease. Prof. Hafezi pointed to a run of recent ELZA papers.

  • The second-generation ELZA-sub400 protocol (American Journal of Ophthalmology) treats ultra-thin corneas with individualised UV doses of up to 10 J/cm². At 12 months, 22 of 29 eyes (76%) showed no progression, and no eye developed endothelial decompensation. In this severely affected group, spectacle-corrected vision declined. The change was not statistically significant, but the authors say it needs confirming in larger studies.
  • The five-year follow-up of the first-generation ELZA-sub400 protocol was led by Dr. Emilio A. Torres-Netto and published in the Journal of Refractive Surgery (JRS). Of 39 ultra-thin corneas, 84.6% remained stable or flattened, again with no endothelial decompensation. Of those 39 eyes, 18 completed the full five years of follow-up.
  • Two laboratory studies of ECO-CAIRS appeared in the Journal of Cataract and Refractive Surgery. In ECO-CAIRS, ring segments of donor cornea are cross-linked outside the eye, then implanted to flatten a keratoconic cornea. In pig corneas, ultra-high-fluence cross-linking at 30 or 60 J/cm² stiffened the tissue more than 10 J/cm². It also changed how the segments dried out and took up water again, which may make them easier to handle and implant.
  • The 1-year clinical results of the ELZA epi-on protocol, published in JRS days before the congress.

What makes the ELZA epi-on protocol different

Standard “epi-off” CXL, the Dresden protocol, removes the central 8–9 mm of epithelium. This lets riboflavin reach the stroma, the thick middle layer of the cornea. Removing the epithelium can cause pain, delayed healing, infection and haze. Leaving it in place avoids this, but earlier epi-on methods ran into two problems. Too little riboflavin got through the intact surface. In addition, too little oxygen reached the stroma, and oxygen is essential to the cross-linking reaction.

Other groups have tackled this with iontophoresis, which drives riboflavin in with a weak electric current, or with extra oxygen. Both add equipment and complexity. The ELZA protocol uses neither. Instead, it combines three elements. A modified penetration-enhancer solution helps riboflavin pass through the epithelium. UV-A light pulsed on and off every second lets oxygen diffuse back into the tissue. Finally, a higher UV dose makes up for the light the epithelium absorbs.

“It’s an epi-on without iontophoresis and without oxygen,” Prof. Hafezi said. “I think that’s the biggest message we have from our Institute.”

What the 1-year results showed

The study treated 38 eyes of 29 patients at the ELZA Institute. Most eyes (27) received 8.1 J/cm² of UV-A at 18 mW/cm², while earlier patients received 7.0 J/cm². After 12 months, maximum keratometry (Kmax, a measure of cone steepness) was unchanged at 56.12 D before and 56.11 D after. Corneal thickness and the other shape measurements also showed no significant change. No patient developed haze, infection, epithelial defects or other complications.

The authors are clear about the limits. The study had no epi-off control group and was not randomised. It also reports corneal shape, not visual acuity or patient-reported outcomes. Longer follow-up and randomised comparisons with epi-off CXL are still needed. They also point out that most of the roughly 54-minute procedure is eye-drop application, which technicians can manage. As a result, they see potential for office-based epi-on cross-linking.

An institute that is growing

Nikki Hafezi focused on ELZA’s development as an organisation. “We have two clinics now, and we’re looking to grow also in Central Asia,” she said. More than 300 companies exhibited at ESCRS this year, from the United States to China. She looked forward to meeting industry partners, clinicians and researchers “to see how we can improve our standard of care as well as our technological advancements in our clinic.”

Learn more

ELZA’s full congress programme is summarised in the highlights from ESCRS 2026 in London. For background on the treatment, see ELZA’s pages on epi-on versus epi-off cross-linking and cross-linking for thin corneas. The ELZA epi-on protocol is offered to patients at the ELZA Institute. Anyone who wants to know whether it suits them can book a consultation.

References

  • Hafezi F, Aydemir ME, Hillen M, et al. Epithelium-on corneal cross-linking using a modified penetration enhancer without supplemental oxygen or iontophoresis. J Refract Surg. 2026. doi:10.3928/1081597X-20260802-01
  • Torres-Netto EA, Kling S, Akcan RE, et al. Five-year follow-up of the ELZA-sub400 protocol. J Refract Surg. 2026. doi:10.3928/1081597X-20260728-01
  • Aydemir ME, Kollros L, Hillen M, et al. Biomechanical stiffening effect in ultra-high-fluence extracorporeal cross-linked corneal allogenic intrastromal ring segments. J Cataract Refract Surg. 2026. doi:10.1097/j.jcrs.0000000000001981
  • Kollros L, Aydemir ME, Boote C, et al. Dehydration and rehydration behavior of ultra-high-fluence extracorporeal cross-linked corneal allogenic intrastromal ring segments (ECO-CAIRS). J Cataract Refract Surg. 2026. doi:10.1097/j.jcrs.0000000000002015
  • Hafezi F, Akcan RE, Kling S, et al. Second-generation ELZA-sub400 protocol: individualized high-fluence cross-linking for ultra-thin keratoconus corneas. Am J Ophthalmol. 2026;290:318-328. doi:10.1016/j.ajo.2026.06.034