Keeping the Cornea Hydrated during CXL: Riboflavin or PBS?

It has been quite the debate. Should surgeons drop riboflavin onto the cornea during the UV irradiation part of a corneal cross-linking (CXL) procedure, or phosphate-buffered saline (PBS)? Simply put: riboflavin or PBS?

Let’s step back. CXL involves the surgeon saturating the structural layer of the cornea, the stroma, with riboflavin. The surgeon then irradiates the stroma with UV light, which causes a photochemical reaction to occur. The reaction between the UV light and riboflavin creates reactive oxygen species, which then immediately react with molecules in the stroma to cross-link them together, which strengthens the cornea. It also consumes the riboflavin, which means as the irradiation proceeds, the UV light reacts with riboflavin that is deeper and deeper in the cornea, thereby strengthening it in those regions.

The reason the surgeon drops a liquid onto the cornea during irradiation is that the patient’s eye is kept open with a speculum, and as the patient cannot blink, fluid evaporates from they eye – so much so that the cornea can actually become slightly thinner during this part of the procedure. But what should the surgeon use to keep the cornea hydrated? Riboflavin or PBS? PBS is simple, inexpensive, and will function perfectly well to keep the cornea hydrated. On the other hand, although it is far more expensive than PBS, riboflavin might be a better option as it can replenish the riboflavin that has been consumed by the UV light. But then, this raises another question: does replenishing riboflavin at the top of the cornea constrict the cross-linking effect to uppermost part of the cornea? Does this affect the strengthening effect?

A team of researchers from the ELZA Institute decided to find out, and they compared the corneal strengthening effect of CXL where riboflavin was used to hydrate the cornea during UV irradiation, with the strengthening effect of CXL when PBS was used for hydration (1). What they found was clear: it doesn’t matter whether the surgeon uses PBS or riboflavin for hydration. The strengthening effect was the same. What this means for clinical practice is also clear. Given PBS is considerably cheaper than riboflavin (and also less messy in the OR!) then choosing PBS to hydrate is a simple and cost-effective choice to make.


Corneal strength measuring apparatus in Prof. Hafezi’s laboratory at the Ocular Cell Biology group at the Center for Applied Biotechnology and Molecular Medicine at the University of Zurich.




  1. Abdshahzadeh H, Abrishamchi R, Aydemir ME, et al. Repeated application of riboflavin during corneal cross-linking does not improve the biomechanical stiffening effect ex vivo. Experimental Eye Research. 2022;224:109267. doi:10.1016/j.exer.2022.109267

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