Corneal cross-linking (CXL) can halt keratoconus, a disease in which the cornea thins and bulges into a cone. However, the treatment needs a UV lamp, sterile riboflavin drops and a trained surgeon. Much of the world has none of those. That gap has made a far simpler idea attractive: swap the lamp for the sun, and the drops for a vitamin B2 tablet. A new ELZA study has now tested that idea in living eyes. It found that oral riboflavin and sunlight do not stiffen the cornea at all.

The study was led by first author Dr. Emilio Torres-Netto, with senior author Prof. Farhad Hafezi. It appears in the August 2026 issue of the Journal of Refractive Surgery.

Why sunlight cross-linking is such an appealing idea

CXL was first described in 2003. Since then, it has become the standard of care for stopping keratoconus from progressing. The mechanism is photochemical. Riboflavin (vitamin B2) soaks into the corneal stroma, absorbs ultraviolet light, and drives a reaction that stiffens the tissue.

Because the reaction needs both the vitamin and a UV source, access depends on equipment and training. It therefore remains limited in low-resource settings and remote regions. In 2019, a small observational report from the United States offered an alternative. High-dose oral riboflavin plus 15 minutes of direct sun each day, it suggested, might stabilise keratoconus. However, that report carried no biomechanical measurements.

ELZA’s own laboratory work had already shown that sunlight can do the job in principle. In a 2023 study, porcine corneas were stripped of their epithelium, soaked in riboflavin and exposed to sunlight. They stiffened about as much as they do with conventional CXL. Even so, the open question was whether the same effect survives in a living eye, with an intact epithelium and a swallowed vitamin.

How the study was done

The team ran a prospective, controlled in vivo study in 16 male New Zealand White rabbits (32 eyes). The Zurich Cantonal Veterinary Office approved the protocol. In the first step, four rabbits (8 eyes) received oral riboflavin at 6 mg/kg per day for 14 days. Two-photon fluorescence microscopy then quantified how much riboflavin had reached the stroma.

In the second step, 12 rabbits (24 eyes) were randomised 1:1. One group followed the oral riboflavin and sunlight protocol; the other received sunlight alone. Animals went outdoors for 15 minutes daily until a cumulative dose of 2,700 klux·h had been delivered. That figure matches the exposure reported in the human observations. Corneal stiffness was then measured two ways: by uniaxial stress–strain extensometry, and by OCT elastography. The latter maps how much the tissue deforms under a small pressure change.

Oral riboflavin and sunlight did not stiffen the cornea

Extensometry found no difference at all between the groups. Stress at 0.1 strain was 152 ± 11.5 kPa in control eyes, and 146 ± 7.0 kPa in treated eyes (p = 0.57). Similarly, the mean elastic modulus between 0.1 and 0.2 strain was 4.1 MPa versus 4.0 MPa (p = 0.870).

In contrast, OCT elastography pointed, if anything, the other way. Strain in the posterior half of the cornea was significantly higher in treated eyes than in controls (5.51‰ versus 3.98‰, p = 0.039). That is consistent with a small reduction in stiffness rather than an increase. The authors interpret it cautiously. It may reflect UV-induced stromal degradation, or subthreshold photochemical effects, rather than any form of cross-linking.

OCT elastography strain across the corneal thickness, from the front surface (0) to the back surface (1). Treated eyes showed more strain in the posterior cornea, not less.
OCT elastography strain across the corneal thickness, from the front surface (0) to the back surface (1). Treated eyes showed more strain in the posterior cornea, not less.

Why the dose never came close

The explanation lies in the numbers. First, mean stromal riboflavin after oral dosing was just 0.000081%. That is roughly 494 times lower than the 0.04% topical drops achieve at a stromal depth of 400 µm. Second, the absorbed UV fluence works out at about 4.3 mJ/cm², some 1,000 times less than the Dresden protocol delivers. In addition, the intact epithelium limits UV penetration and the oxygen supply the reaction depends on. The failure, in other words, is one of bioavailability rather than photochemistry.

Why the finding matters outside the laboratory

Meanwhile, several commercial ventures promote oral riboflavin and sunlight as a keratoconus treatment. Keratoconus progresses while it is untreated, so an ineffective substitute is not a neutral choice. It can delay established therapy long enough for irreversible vision loss to occur.

Still, the authors are careful about what their data do and do not cover. They tested a standalone cross-linking effect. The study does not address nutritional supplementation, riboflavin deficiency, or any antioxidant role in the disease. Simplified cross-linking also remains a goal worth pursuing, particularly where conventional CXL is out of reach. The route there, the authors suggest, runs through better topical delivery and through light sources tuned to the absorption spectrum of riboflavin.

About the study

This work was supported in part by the Light for Sight Foundation (Dietikon, Switzerland) and the VELUX Stiftung (Zurich, Switzerland). Nikki Hafezi is CEO of EMAGine AG. Prof. Farhad Hafezi is co-inventor on patent applications covering corneal cross-linking technology. He is also Chief Scientific Officer of EMAGine AG and holds stock or stock options in the company. The remaining authors declared no competing interests. Cross-linking for keratoconus is performed at ELZA’s clinics in Zurich and Dietikon.

Further reading on the ELZA site

References